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What Is Nanoscale

 

 

 

Nanomaterials and nanoparticles- sources and toxicity

Study improves understanding of method for creating multi-metal nanoparticles---

Evolution of a bimetallic nanocatalyst

Lungs may suffer when certain elements go nano

Are silver nanoparticles harmful?--

 Toxic nanoparticles might be entering human food supply

New Insights Into Health And Environmental Effects Of Carbon Nanoparticles

Researchers are reporting that carbon nanoparticles can be transmitted by fruit flies and that certain nanoparticles can be toxic to adult flies

.--- Scientists use laser imaging to assess safety of zinc oxide nanoparticles in sunscreen

X-rays reveal uptake of nanoparticles by soybean crops

Evidence that nanoparticles in sunscreens could be toxic if accidentally eaten—

Nanoparticle thin films that self-assemble in one minute

The Art of Self-Assembly

Synthetic and biological nanoparticles combined to produce new metamaterials

Scientists have succeeded in organizing virus particles, protein cages and nanoparticles into crystalline materials

Carbon black particle exhibits size dependent toxicity in human monocytes

SBU-Led Study Reveals Nanoparticles Found in Everyday Items Can Inhibit Fat Storage Increase in gold nanoparticles can accelerate aging and wrinkling, slow wound healing, cause onset of diabetes

Nanoparticles that look and act like cells

Camouflaged nanoparticles (yellow) cloaked in the membranes of white blood cells rest on the surface of an immune system cell (phagocyte, blue) without being recognized, ingested, and destroyed.--

In vitro phototoxicity and hazard identification of nano-scale titanium dioxide.-

 Protein Nanostructures

Polymerization

DNA-linked nanoparticles form switchable 'thin films' on a liquid surface

 

 

 

 

 

 

 

 

 

 

 

 NanosParticle-Activity-Effect-and Hazard

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What is nanoscale?

There is no fixed definition for what nanoscale is, but there are a couple of things that are very important – small size and different properties.

Nanoparticle size

At least one dimension (height, length or depth) is less than 100 nm:

  • A nanotube can be much longer than 100 nm, but it is still called a nanoparticle because it is only about 3 nm wide.
  • A very thin film of material can be many centimetres wide, but if it is less than 100 nm thick, it is still called a nanofilm.

This definition of nanoscale tends to be used by people who create tiny devices such as pumps and motors out of a few atoms, or by people who deal with very thin surface coatings.

Nature of Science

In science, most measurements have a precise definition. Some other scientific terms are not so well defined. A nanometre is a measurement – it is clearly defined as a billionth of a metre. On the other hand, although nanoscale is a scientific term, it means different things to different people.

Many nanoparticles are ball-shaped, so all dimensions are small.

Nanoparticle properties

To many scientists, things are at the nanoscale if they are so small that they display different properties to the large scale material. This mostly happens when particles are only a few nanometres across.

For example, you may know that water boils at 100ºC (at a pressure of 1 atmosphere), but that is only true for large amounts of water. A drop of water only 5 nm across boils at 95.9ºC.

One nanoparticle can behave differently to another nanoparticle even if it is only slightly a different size. It may be a different colour, it may have a different melting point, or it may conduct electricity differently.

So, there is more than one definition of what is meant by nanoscale. Learning to understand and make use of these different properties of matter at the nanoscale is what nanoscience is about.

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Part 1. General introduction to nanoscience and commonly used terms explained

·         The prefix 'nano' in the context of the definitions-descriptions given below, and used on this webpage, usually refers to dimensions-size of 1 - 100 nm. i.e. of nanoscale.

o        nm is the accepted abbreviation for nanometre (nanometer) - more on the relative size of molecules and bigger particles is given further down in a size comparison data table to put the nanoscale 'scene' in perspective.

·         What is Nanoscience? Nanoscience is the branch of science concerned with the development and production and uses of materials whose basic components are of nanoscale size, i.e. ~1 - 100 nm in size. Other more specific terms which come under the general term 'nanoscience' are described in more detail, particularly the term nanochemistry.

·         What is Nanotechnology? Nanotechnology involves methods for transforming matter, energy and information based on nanometer scale (nanosized) components with particular defined molecular features and prescribed physical and chemical properties.

o        It involves techniques that produces materials with characteristic features with particle sizes of ~1 - 100 nm and involves advanced microfabrication techniques.

o        Nanotechnology is still based on manufacturing processes that use typical chemical and mechanical principles BUT in novel and unfamiliar situations (at least to those of us who were graduate students in the late 60s!).

o        Nanotechnology creates and uses structures that have novel properties because of their nanoscale small size.

o        Nanotechnology is developing from the ability to control and manipulate at the atomic scale, which essentially means controlling situations at the atomic and molecular level, far removed from normal processing of bulk materials in a typical laboratory or industrial process.

o        The use of the scanning tunnelling microscope allows us to 'see' individual atoms in an atomic or molecular lattice in a way that was inconceivable a 100 years ago when the principles of atomic and molecular structure were being discovered.

§         So, it is now possible to see and investigate nanoscale structures at the atomic-molecular level and this 'feedback' enables you to compare the actual structure with the desired designed structure which eventually you would hope to have the prescribed desirable properties.

§         Does this advanced technology blur the distinction between computer simulation and reality?

§         We are now well into CAD (computer aided design) at the molecular level and there doesn't seem to any limit (within the laws and principles of chemistry) as to what structures we can build.

o        The many applications of nanotechnology include the use of semi-conductors that only conduct electricity in specific conditions and allows the design of much very tiny 'devices' normal scale conductors, so the final product can be much smaller, enabling the design and use of faster smaller computers working at the molecular level. It will be/is? possible to make very tiny mechanical devices to perform some task in otherwise inaccessible situations.

·         What are Nanostructures? Nanostructures are material structures assembled from layers or clusters of atoms of nanoscale size i.e. ~1-100 nanometre. By controlling the size and assembling of nanoscale constituents it is possible to alter and control the structure and properties of the final nanostructure. The advantage of these new materials is that they can be designed and built from the atomic level upwards to have specific properties of great use to material scientists, a good example is the ongoing development in the design and use carbon nanotubes.

o        Nanocrystals may consist of over 1000 atoms but it can be quite variable within the 1-100 nm range.

o        The wide applications of such nanostructures includes semi-conductor devices, strained-layer lattices, magnetic multilayers.

o        Nanostructures are built up from atomic or molecular precursors and processed via chemical deposition or physical vapour deposition, gas condensation, chemical precipitation, aerosol reactions and biological templating - a wide range of methods of assembling arrays of atoms.

o        Note that some nanoparticles are created naturally e.g.

§         Very finely suspended mineral particles in water - the tiniest of colloidal particles act as nanoparticles.

§         During inefficient combustion of organic molecules e.g. fossil fuels or plastics, nanosized particles of soot (mainly carbon) are formed.

§         Evaporated seaspray can produce nanoscale salt particles.

·         What are Nanomaterials? Nanomaterials is a general word for any material that has a composition based on nanoparticle units e.g. nanoparticles of silver, carbon nanotubes, inorganic ceramic materials etc. more examples

·         NANOPARTICLES

o        As already mentioned nanoparticles are usually in the size range of 1 to 100 nm, described as being of nanoscale

o        Nanoparticles can be made of elements, organic molecules, inorganic compounds, inorganic cluster compounds or metallic/semi-conductor (maybe ~'semi-metal') particles.

o        Nanoparticles have a high surface to volume ratio which has a dramatic effect on their properties compared to non-nanoscale forms of the same material.

o        As a point of comparison, since nanoparticles are in the size range 1 - 100 nm, a human hair is 0.05 to 0.1 mm (50000 -100000 nm) in diameter, in other words nanoparticles are usually 500 - 100000 times 'thinner' than a human hair!

o        1 nanometre (US nanometer), 1 nm = 10-9 of a metre (0.000 000 001 m, pretty small!)

§         Compared to other units:

§         1 cm = 10-2 m  (1 cm = 10000000 nm)

§         1 mm = 10-3 m  (1 millimetre = 1000000 nm)

§         1 μm = 10-6 m  (1 micrometre = 1000 nm)

§         1 nm = 10-9 m

§         1 pm = 10-12 m  (1 picometre = 0.001 nm)

o        So, when talking nanoscale science, we are talking about pretty small structures!

o        More 'chemical structure' points of comparison are given in the table below.

o        To put nanoparticles in 'size' or 'dimension' perspective, consider the table below of 'materials' - pure elements, pure compounds and other more complex materials etc.

  • Notes on the table
      1. Carbon is the basic atom or unit of carbon nanotubes.
      2. Sulfur is a typical non-metal atom.
      3. Water is a relatively small molecule, one of the smallest in fact.
      4. Silver is typical metallic lattice or huge array of atoms, titanium dioxide is a giant lattice ionic lattice.
      5. Glucose is a molecule of 24 combined atoms of carbon, hydrogen and oxygen atoms.
      6. Fullerene-60, a 'bucky ball', is the precursor structure on which carbon nanotubes are based.
      7. A simple protein is a polymer of alpha-amino acids [H2HCH(R)COOH]n where R is of variable structure, n is a large number of peptide units-residues.
      8. Assume silver or titanium dioxide nanoparticles are ~spherical
      9. A virus is a very simple organism, the simplest of which consists of a strand of RNA in a protein sheath.
      10. A typical carbon nanotube might have a radius of 3 nm and up to 100 nm long.
      11. The wavelengths of visible light are typically 4 to 700 times bigger than most nanoparticles!
      12. A bacterium is a usually a single celled cellular micro-organism and can contain over 5000 different molecules and ions.
      13. A eukarytic cell is what all multi-celled higher organisms are made up of.
      14. The human hair is easily recognised as strands of a pretty thin material.

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NANOPARTICLES---

 

The prefix-nano is derived from the Greek word nanos meaning dwarf  Nanotechnology involves the manipulation and application of engineered particles or systems that have at least one dimension lessthan 100 nanometers (nm) in length (Hoyt and Mason, 2008). The term nanoparticles applies only to engineered particles (such as metal oxides, carbon nanotubes, fullerenes etc.) and does not apply to particles under 100 nm that occur naturally or are by-products of other processes such as welding fumes, fire smoke, or carbon black

 

 

A number of studies have reported that AgNPs[F1]  may induce cytotoxicity in phagocytosing cells, such as not only mouse peritoneal macrophages but also human monocytes [38–40]. Further studies suggested that the cytotoxic effects were induced by reactive oxygen species (ROS) resulting in cellular apoptosis, at least low concentrations and short incubation times [37, 41–43]. The production of ROS has also been implicated in DNA damage caused by AgNPs, which was reported in a number of in vitro studies [27, 38, 44]. Caspase-3 is one of the key molecules in apoptosis, and its activation is often considered as the point of no return in apoptosis [45]. Activation of caspase-3 results in the cleavage of (inhibitor of caspase-activated DNAse) ICAD and translocation of (caspase activated DNAse) CAD to the nucleus, ultimately resulting in DNA fragmentation. The most prominent event in the early stages of apoptosis is internucleosomal DNA cleavage by endonuclease activities [46]. Previous studies suggested that AgNPs treated cancer cell, and noncancer cells revealed enhanced caspase-3 activity and formation of significant DNA laddering [14, 15, 47].

 

Nanomaterials and nanoparticles- sources and toxicity.

Buzea C1, Pacheco II, Robbie K.

Author information

Abstract

This review is presented as a common foundation for scientists interested in nanoparticles, their origin,activity, and biological toxicity. It is written with the goal of rationalizing and informing public health concerns related to this sometimes-strange new science of "nano," while raising awareness of nanomaterials' toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to tiny particles via dust storms, volcanic ash, and other natural processes, and that our bodily systems are well adapted to protect us from these potentially harmful intruders. There ticuloendothelial system, in particular, actively neutralizes and eliminates foreign matter in the body,including viruses and nonbiological particles. Particles originating from human activities have existed for millennia, e.g., smoke from combustion and lint from garments, but the recent development of industry and combustion-based engine transportation has profoundly increased an thropogenic particulate pollution. Significantly, technological advancement has also changed the character of particulate pollution, increasing the proportion of nanometer-sized particles--"nanoparticles"--and expanding the variety of chemical compositions[F2] . Recent epidemiological studies have shown a strong correlation between particulate air pollution levels, respiratory and cardiovascular diseases, various cancers, and mortality. Adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape,agglomeration state, and electromagnetic properties. Animal and human studies show that inhaled nanoparticles are less efficiently removed than larger particles by the macrophage clearance mechanisms in the lungs, causing lung damage, and that nanoparticles can translocate through the circulatory, lymphatic, and nervous systems to many tissues and organs, including the brain. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function.Examples of toxic effects include tissue inflammation, and altered cellular redox balance toward oxidation, causing abnormal function or cell death. The manipulation of matter at the scale of atoms,"nanotechnology," is creating many new materials with characteristics not always easily predicted from current knowledge. Within the nearly limitless diversity of these materials, some happen to be toxic to biological systems, others are relatively benign, while others confer health benefits. Some of these materials have desirable characteristics for industrial applications, as nanostructured materials often exhibit beneficial properties, from UV absorbance in sunscreen to oil-less lubrication of motors.A rational science-based approach is needed to minimize harm caused by these materials, while supporting continued study and appropriate industrial development. As current knowledge of the toxicology of "bulk" materials may not suffice in reliably predicting toxic forms of nanoparticles,ongoing and expanded study of "nanotoxicity" will be necessary. For nanotechnologies with clearly associated health risks, intelligent design of materials and devices is needed to derive the benefits of these new technologies while limiting adverse health impacts. Human exposure to toxic nanoparticles can be reduced through identifying creation-exposure pathways of toxins, a study that may someday soon unravel the mysteries of diseases such as Parkinson's and Alzheimer's. Reduction in fossil fuel combustion would have a large impact on global human exposure to nanoparticles, as would limiting deforestation and desertification.While nanotoxicity is a relatively new concept to science, this review reveals the result of life's long history of evolution in the presence of nanoparticles, and how the human body, in particular, has adapted to defend itself against nanoparticulate intruders.

2007 American Vacuum Society.

Evolution of a bimetallic nanocatalyst

Date:

June 6, 2014

Source:

DOE/Lawrence Berkeley National Laboratory

TEM image of platinum/cobalt bimetallic nanoparticle catalyst in action shows that during the oxidation reaction, cobalt atoms migrate to the surface of the particle, forming a cobalt oxide epitaxial film, like water on oil.---Atomic-scale snapshots of a bimetallic nanoparticle catalyst in action have provided insights that could help improve the industrial process by which fuels and chemicals are synthesized from natural gas, coal or plant biomass. A multi-national lab collaboration led by researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) has taken the most detailed look ever at the evolution of platinum/cobalt bimetallic nanoparticles during reactions in oxygen and hydrogen gases.--"Using in situ aberration-corrected transmission electron microscopy (TEM), we found that during the oxidation reaction, cobalt atoms migrate to the nanoparticle surface, forming a cobalt oxide epitaxial film, like water on oil," says Haimei Zheng, a staff scientist in Berkeley Lab's Materials Sciences Division who led this study. "During the hydrogen reduction reaction, cobalt atoms migrate back into the bulk, leaving a monolayer of platinum on the surface. This atomic information provides an important reference point for designing and engineering better bimetallic catalysts in the future."--Bimetallic catalysts are drawing considerable attention from the chemical industry these days because in many cases they offer superior performances to their monometallic counterparts. There is also the possibility of tuning their catalytic performances to meet specific needs. A bimetallic catalyst of particular interest entails the pairing of platinum, the gold standard of monometallic catalysts, with cobalt, a lesser catalyst but one that is dramatically cheaper than platinum. The platinum/cobalt catalyst is not only considered a model system for the study of other bimetallic nanocatalysts, it is also an excellent promoter of the widely used Fischer-Tropsch process, in which mixtures of hydrogen and carbon monoxide are converted into long-chain carbons for use as fuels or in low-temperature fuel cells.

"While there have been many studies on platinum/cobalt and other bimetallic catalysts, information on how reactions proceed atomically and what the morphology looks like has been missing," Zheng says. "To acquire this information it was necessary to map the atomic structures in reactive environments in situ, which we did using specially equipped TEMs."--The in situ environmental TEM experiments were carried out at both the Environmental Molecular Sciences Laboratory, which is located at PNNL, and at BNL's Center for Functional Nanomaterials. Ex situ aberration-corrected TEM imaging was done at Berkeley Lab's National Center for Electron Microscopy using TEAM 0.5, the world's most powerful TEM.--"This work is an excellent example of collaborative team-work among multiple institutes," Zheng says. "Having access to such high-end resources and being able to form such close team collaborations strengthens our ability to tackle challenging scientific problems."--The in situ aberration corrected TEM studies of Zheng and her colleagues revealed that because of a size mismatch between the lattices of the cobalt oxide epitaxial film and the platinum surface, the cobalt oxide lattice is compressively strained at the interface to fit on the platinum lattice[F3] . As the strain energy relaxes, the cobalt oxide film starts breaking up to form distinct molecular islands on the platinum surface. This reduces the effective reaction surface area per volume and creates catalytic voids, both of which impact overall catalytic performance.--"By taking this segregation of the platinum and cobalt atoms into consideration, the interfacial strain that arises during oxidation can be predicted," Zheng says. "We can then design nanoparticle catalysts to ensure that during reactions the material with higher catalytic performance will be on surface of the nanoparticles."--Zheng adds that the ability to observe atomic scale details of the evolution of the structure of nanoparticles in their reactive environments not only opens the way to a deeper understanding of bimetallic nanoparticle catalysis, it also allows for the study of a wider variety of nanoparticle systems where reaction pathways remain elusive.--This research was supported by the DOE Office of Science. It made use of the resources at the Environmental Molecular Sciences Laboratory, the Center for Functional Nanomaterials, and the National Center for Electron Microscope, user facilities supported by DOE's Office of Science.--Story Source--The above story is based on materials provided by DOE/Lawrence Berkeley National Laboratory. Note: Materials may be edited for content and length.--Journal Reference-Huolin L. Xin, Selim Alayoglu, Runzhe Tao, Arda Genc, Chong-Min Wang, Libor Kovarik, Eric A. Stach, Lin-Wang Wang, Miquel Salmeron, Gabor A. Somorjai, Haimei Zheng. Revealing the Atomic Restructuring of Pt–Co Nanoparticles. Nano Letters, 2014; 140519100039000 DOI: 10.1021/nl500553a

 

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Study improves understanding of method for creating multi-metal nanoparticles

Date:

December 16, 2010

Source:

North Carolina State University

This diagram shows how researchers created the core/shell nanoparticles, and alloy nanoparticles, from gold and silver.--A new study from researchers at North Carolina State University sheds light on how a technique that is commonly used for making single-metal nanoparticles can be extended to create nanoparticles consisting of two metals -- and that have tunable properties. The study also provides insight into the optical properties of some of these nanoparticles.-Tuning the optical properties of nanoparticles is of interest for applications such as security technology, and for use in making chemical reactions more efficient [F4] -- which has multiple industrial and environmental applications.-The researchers created core/shell nanoparticles with a gold core and silver shell, as well as alloy nanoparticles, which mix the gold and silver. The researchers also characterized the optical properties of these nanoparticles. "Silver and gold have unique optical properties arising from their specific interactions with the electric field of light," says Dr. Joe Tracy, an assistant professor of materials science and engineering at NC State and co-author of a paper describing the study. "By manipulating the ratio of the metals, and whether the nanoparticles have core/shell or alloy structures, we can alter their optical properties with control."-The researchers synthesized the nanoparticles using a technique called "digestive ripening." The technique has been used to create single-metal particles for approximately a decade, but there have been limited studies of core/shell and alloy nanoparticles created using digestive ripening. However, the comprehensive nature of this study may make it more common.-"This study, along with related work by others, shows that digestive ripening is a viable method for creating multi-component metal nanoparticles. We used gold and silver, but the same principles would likely apply to other metals," Tracy says. "Our detailed evaluation of this synthetic approach should help other researchers explore other kinds of binary metal nanoparticles."-Digestive ripening relies on the use of ligands, which are small organic molecules with parts that bond directly to metals. The ligands are usually anchored to the metal cores of the nanoparticles and prevent the nanoparticles from clumping together, which allows them to be suspended in solution[F5] . Digestive ripening occurs when the ligands are able to transport metal atoms from the core of one nanoparticle to another -- resulting in a more homogenous size distribution among the nanoparticles.-The researchers used digestive ripening to create a solution of gold nanoparticles of similar size. When they introduced silver acetate into the solution, the ligands transported silver atoms to the surfaces of the gold nanoparticles, resulting in nanoparticles with gold cores and silver shells.-Researchers then transferred the nanoparticles into a second solution, containing a different ligand. Heating this second solution to 250 degrees Celsius caused the metals to diffuse into each other -- creating nanoparticles made of a gold-silver alloy.-The researchers also created gold-silver alloy nanoparticles by skipping the shell-creation step, introducing silver acetate into the second solution, and raising the temperature to 250 degrees Celsius. This "shortcut" method has the benefit of simplifying control over the gold-to-silver ratio of the alloy.-The paper, "Synthesis of Au(core)/Ag(shell) Nanoparticles and their Conversion to AuAg Alloy Nanoparticles," was published online Dec. 13 by the journal Small. The research was funded by the National Science Foundation and NC State. The lead author of the paper is Matthew Shore, who was an undergraduate at NC State when the research was done. Co-authors include Tracy, NC State Ph.D. student Aaron Johnston-Peck, former NC State postdoc Dr. Junwei Wang, and University of North Carolina at Chapel Hill assistant professor Dr. Amy Oldenburg.-NC State's Department of Materials Science and Engineering is part of the university's College of Engineering.-Story Source-The above story is based on materials provided by North Carolina State University. Note: Materials may be edited for content and length.-Journal Reference-Matthew S. Shore, Junwei Wang, Aaron C. Johnston-Peck, Amy L. Oldenburg, Joseph B. Tracy. Synthesis of Au(Core)/Ag(Shell) Nanoparticles and their Conversion to AuAg Alloy Nanoparticles. Small, 2010; DOI: 10.1002/smll.201001138

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Lungs may suffer when certain elements go nano

Date:

January 27, 2014

Source:

Missouri University of Science and Technology-Nanoparticles are used in all kinds of applications -- electronics, medicine, cosmetics, even environmental clean-ups. More than 2,800 commercially available applications are now based on nanoparticles, and by 2017, the field is expected to bring in nearly $50 billion worldwide.

But this influx of nanotechnology is not without risks, say researchers at Missouri University of Science and Technology.-"There is an urgent need to investigate the potential impact of nanoparticles on health and the environment," says Yue-Wern Huang, professor of biological sciences at Missouri S&T.-Huang and his colleagues have been systematically studying the effects of transition metal oxide nanoparticles on human lung cells. These nanoparticles are used extensively in optical and recording devices, water purification systems, cosmetics and skin care products, and targeted drug delivery, among other applications.-"In their typical coarse powder form, the toxicity of these substances is not dramatic[F6] ," says Huang. "But as nanoparticles with diameters of only 16-80 nanometers, the situation changes significantly."-The researchers exposed both healthy and cancerous human lung cells to nanoparticles composed of titanium, chromium, manganese, iron, nickel, copper and zinc compounds -- transition metal oxides that are on the fourth row of the periodic table. The researchers discovered that the nanoparticles' toxicity to the cells, or cytotoxicity, increased as they moved right on the periodic table.-"About 80 percent of the cells died in the presence of nanoparticles of copper oxide and zinc oxide,"[F7]  says Huang. "These nanoparticles penetrated the cells and destroyed their membranes. The toxic effects are related to the nanoparticles' surface electrical charge and available docking sites."-Huang says that certain nanoparticles released metal ions -- called ion dissolution -- which also played a significant role in cell death.-Huang is now working on new research that may help reduce nanoparticles' toxicity and shed light on how nanoparticles interact with cells.--"We are coating toxic zinc oxide nanoparticles with non-toxic nanoparticles to see if zinc oxide's toxicity can be reduced," Huang says. "We hope this can mitigate toxicity without compromising zinc oxide's intended applications. We're also investigating whether nanoparticles inhibit cell division and influence cell cycle."--The researchers' findings, "Cytotoxicity in the age of nano: The role of fourth period transition metal oxide nanoparticle physicochemical properties," were published in the Nov. 25, 2013, issue of the journal Chemico-Biological Interactions.--Story Source-The above story is based on materials provided by Missouri University of Science and Technology. Note: Materials may be edited for content and length.--Journal Reference-Yue-Wern Huang et al. Cytotoxicity in the age of nano: The role of fourth period transition metal oxide nanoparticle physicochemical properties. Chemico-Biological Interactions, January 2014

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Are silver nanoparticles harmful?

Date:

March 14, 2012

Source:

Norwegian Institute of Public Health

Silver nanoparticles cause more damage to testicular cells than titanium dioxide nanoparticles, according to a recent study by the Norwegian Institute of Public Health. However, the use of both types may affect testicular cells with possible consequences for fertility.--Commonly used---Nanotechnology is increasingly used in consumer products, medicines and building products. The potential risks of using engineered nanoparticles need to be monitored so that the industry can develop products that are safe for humans and nature.--Previous research has shown that nanoparticles can cross both the blood-brain barrier and blood-testes barrier in mice and rats, and are taken up by cells. This study aimed to see if silver and titanium dioxide nanoparticles had any effect on human and mice testicular cells.--The researchers found that silver nanoparticles had a toxic effect on cells, suppressing cellular growth and multiplication and causing cell death depending on concentrations and duration of exposure. The effect was weaker for titanium dioxide nanoparticles, although both types did cause cell type-specific DNA damage, with possible implications on reproduction as well as human and environmental health.--"It seems that the type of nanoparticle, and not the size alone, may be the limiting factor" says Nana Asare, primary author of the study published in Toxicology.--Further studies using in vivo models are needed to study the impact of nanoparticles on reproductive health.--The researchers used cells from a human testicular carcinoma[F8]  cell line and testicular cells from two strains of mice, one of which is genetically modified to serve as a representative model for human male reproductive toxicity. The cells were exposed to titanium dioxide nanoparticles (21nm) and two different sizes of silver nanoparticles (20 nm and 200nm) over different concentrations and time periods. Both sizes of silver nanoparticles inhibited normal cell function and caused more cell death than the titanium dioxide nanoparticles. In particular, the 200 nm silver particles caused a concentration-dependent increase in DNA damage in the human cells.

Nano facts

  • Nanotechnology is technology on the atomic and molecular scale
  • A nanometre (nm) is one billionth of a metre
  • A nanoparticle is a particle with one or more external dimensions in the size range 1 nm -- 100 nm
  • The aspect ratio between a nanoparticle and a football is similar to that between a football and Earth
  • Nanotechnology is working on a scale of 100 nm (which corresponds approximately to the size of a virus) down to the size of atoms, about 0.1 nm
  • Nano-scale materials and processes are present in nature, ranging from free molecules in gases and liquids to proteins and organic processes
  • Some substances are produced unintentionally, such as welding dust and diesel particulates

Story Source-The above story is based on materials provided by Norwegian Institute of Public Health. Note: Materials may be edited for content and length.--Journal Reference-Nana Asare, Christine Instanes, Wiggo J. Sandberg, Magne Refsnes, Per Schwarze, Marcin Kruszewski, Gunnar Brunborg. Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology, 2012; 291 (1-3): 65 DOI: 10.1016/j.tox.2011.10.022

 

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Toxic nanoparticles might be entering human food supply

Date:

August 22, 2013

Source:

University of Missouri-Columbia

Graduate student Zhong Zhang applies silver nanoparticles to a piece of fruit. In a recent study, University of Missouri researchers found that these particles could pose a potential health risk to humans and the environment.-Over the last few years, the use of nanomaterials for water treatment, food packaging, pesticides, cosmetics and other industries has increased. For example, farmers have used silver nanoparticles as a pesticide because of their capability to suppress the growth of harmful organisms[F9] . However, a growing concern is that these particles could pose a potential health risk to humans and the environment. In a new study, researchers at the University of Missouri have developed a reliable method for detecting silver nanoparticles in fresh produce and other food products.-"More than 1,000 products on the market are nanotechnology-based products," said Mengshi Lin, associate professor of food science in the MU College of Agriculture, Food and Natural Resources. "This is a concern because we do not know the toxicity of the nanoparticles. Our goal is to detect, identify and quantify these nanoparticles in food and food products and study their toxicity as soon as possible."-Lin and his colleagues, including MU scientists Azlin Mustapha and Bongkosh Vardhanabhuti, studied the residue and penetration of silver nanoparticles on pear skin. First, the scientists immersed the pears in a silver nanoparticle solution similar to pesticide application. The pears were then washed and rinsed repeatedly. Results showed that four days after the treatment and rinsing, silver nanoparticles were still attached to the skin, and the smaller particles were able to penetrate the skin and reach the pear pulp.-"The penetration of silver nanoparticles is dangerous to consumers because they have the ability to relocate in the human body after digestion," Lin said. "Therefore, smaller nanoparticles may be more harmful to consumers than larger counterparts."-When ingested, nanoparticles pass into the blood and lymph system, circulate through the body and reach potentially sensitive sites such as the spleen, brain, liver and heart.-The growing trend to use other types of nanoparticles has revolutionized the food industry by enhancing flavors, improving supplement delivery, keeping food fresh longer and brightening the colors of food. However, researchers worry that the use of silver nanoparticles could harm the human body.-"This study provides a promising approach for detecting the contamination of silver nanoparticles in food crops or other agricultural products," Lin said.-Members of Lin's research team also included Zhong Zang, a food science graduate student. The study was published in the Journal of Agricultural and Food Chemistry.-Story Source-The above story is based on materials provided by University of Missouri-Columbia. The original article was written by Diamond Dixon. Note: Materials may be edited for content and length.-Journal Reference-Zhong Zhang, Mengshi Lin, Sha Zhang, Bongkosh Vardhanabhuti. Detection of Aflatoxin M1 in Milk by Dynamic Light Scattering Coupled with Superparamagnetic Beads and Gold Nanoprobes. Journal of Agricultural and Food Chemistry, 2013; 61 (19): 4520 DOI: 10.1021/jf400043z

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New Insights Into Health And Environmental Effects Of Carbon Nanoparticles

Date:

August 6, 2009

Source:

American Chemical Society

Researchers are reporting that carbon nanoparticles can be transmitted by fruit flies and that certain nanoparticles can be toxic to adult flies.

Credit: American Chemical Society

A new study raises the possibility that flies and other insects that encounter nanomaterial "hot spots," or spills, near manufacturing facilities in the future could pick up and transport nanoparticles on their bodies, transferring the particles to other flies or habitats in the environment. ---The study on carbon nanoparticles — barely 1/5,000th the width of a human hair —is scheduled for the Aug. 15 issue of ACS' Environmental Science & Technology. -David Rand and Robert Hurt and colleagues note that emergence of a nanotechnology industry is raising concerns about the potential adverse health and environmental effects of nanoparticles. These materials show promise for use in a wide range of products, including cosmetics, pharmaceuticals, and electronics.--The study focused on determining how different kinds of exposure to nanoparticles affected larval and adult fruit flies. Scientists use fruit flies as stand-ins for humans and other animals in certain kinds of research. There were no apparent ill effects on fruit fly larvae that ate food containing high concentrations of nanoparticles. However, adult flies died or were incapacitated when their bodies were exposed to large amounts of certain nanoparticles.--During the experiments, the researchers noted that contaminated flies transferred nanoparticles to other flies, and realized that such transfer could also occur between flies and humans in the future. The transfer involved very low levels of nanoparticles, which did not have adverse effects on the fruit flies. Since larvae can tolerate very high doses of nanoparticles in the diet, but adult flies show very different sensitivities, the environmental impact depends on the ecological context of nanoparticle release.--Story Source-The above story is based on materials provided by American Chemical Society. Note: Materials may be edited for content and length.--Journal Reference-Xinyuan Liu, Daniel Vinson, Dawn Abt, Robert H. Hurt, David M. Rand. Differential Toxicity of Carbon Nanomaterials in Drosophila: Larval Dietary Uptake is Benign, but Adult Exposure Causes Locomotor Impairment and Mortality. Environmental Science & Technology, DOI: 10.1021/es901079z

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Scientists use laser imaging to assess safety of zinc oxide nanoparticles in sunscreen

Date:

December 2, 2011

Source:

Optical Society of America

Overlay of the confocal/multiphoton image of the excised human skin. Yellow color represents skin autofluorescence excited by 405 nm; Purple color represents zinc oxide nanoparticle distribution in skin (stratum corneum) excited by 770 nm, with collagen-induced faint SHG signals in the dermal layer.

Credit: Biomedical Optics Express.

Ultra-tiny zinc oxide (ZnO) particles with dimensions less than one-ten-millionth of a meter are among the ingredients list of some commercially available sunscreen products, raising concerns about whether the particles may be absorbed beneath the outer layer of skin. To help answer these safety questions, an international team of scientists from Australia and Switzerland have developed a way to optically test the concentration of ZnO nanoparticles at different skin depths. They found that the nanoparticles did not penetrate beneath the outermost layer of cells when applied to patches of excised skin. --The results, which were published this month in the Optical Society's (OSA) open-access journal Biomedical Optics Express, lay the groundwork for future studies in live patients.-The high optical absorption of ZnO nanoparticles in the UVA and UVB range, along with their transparency in the visible spectrum when mixed into lotions, makes them appealing candidates for inclusion in sunscreen cosmetics. However, the particles have been shown to be toxic to certain types of cells within the body, making it important to study the nanoparticles' fate after being applied to the skin. By characterizing the optical properties of ZnO nanoparticles, the Australian and Swiss research team found a way to quantitatively assess how far the nanoparticles might migrate into skin.--The team used a technique called nonlinear optical microscopy, which illuminates the sample with short pulses of laser light and measures a return signal. Initial results show that ZnO nanoparticles from a formulation that had been rubbed into skin patches for 5 minutes, incubated at body temperature for 8 hours, and then washed off, did not penetrate beneath the stratum corneum, or topmost layer of the skin. The new optical characterization should be a useful tool for future non-invasive in vivo studies, the researchers write.--Story Source-The above story is based on materials provided by Optical Society of America. Note: Materials may be edited for content and length.-Journal Reference-Zhen Song, Timothy A. Kelf, Washington H. Sanchez, Michael S. Roberts, Jaro Rička, Martin Frenz, Andrei V. Zvyagin. Characterization of optical properties of ZnO nanoparticles for quantitative imaging of transdermal transport. Biomedical Optics Express, 2011; 2 (12): 3321 DOI: 10.1364/BOE.2.003321

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Evidence that nanoparticles in sunscreens could be toxic if accidentally eaten

Date:

April 7, 2010

Source:

American Chemical Society

 

Sunscreens contain nanoparticles of zinc oxide -- used to prevent the damaging effects of sunlight -- that can harm colon cells and may be toxic if accidentally eaten.--Scientists are reporting that particle size affects the toxicity of zinc oxide, a material widely used in sunscreens. Particles smaller than 100 nanometers are slightly more toxic to colon cells than conventional zinc oxide. Solid zinc oxide was more toxic than equivalent amounts of soluble zinc, and direct particle to cell contact was required to cause cell death. Their study is in ACS' Chemical Research in Toxicology, a monthly journal.-Philip Moos and colleagues note that there is ongoing concern about the potential toxicity of nanoparticles of various materials, which may have different physical and chemical properties than larger particles. Barely 1/50,000 the width of a human hair, nanoparticles are used in foods, cosmetics and other consumer products. Some sunscreens contain nanoparticles of zinc oxide. "Unintended exposure to nano-sized zinc oxide from children accidentally eating sunscreen products is a typical public concern, motivating the study of the effects of nanomaterials in the colon," the scientists note.-Their experiments with cell cultures of colon cells compared the effects of zinc oxide nanoparticles to zinc oxide sold as a conventional powder. They found that the nanoparticles were twice as toxic to the cells as the larger particles.-Although the nominal particle size was 1,000 times larger, the conventional zinc oxide contained a wide range of particle sizes and included material small enough to be considered as nanoparticles. The concentration of nanoparticles that was toxic to the colon cells was equivalent to eating 2 grams of sunscreen -- about 0.1 ounce. This study used isolated cells to study biochemical effects and did not consider the changes to particles during passage through the digestive tract. The scientists say that further research should be done to determine whether zinc nanoparticle toxicity occurs in laboratory animals and people.--Story Source-The above story is based on materials provided by American Chemical Society. Note: Materials may be edited for content and length.-Journal Reference-Moos et al. ZnO Particulate Matter Requires Cell Contact for Toxicity in Human Colon Cancer Cells. Chemical Research in Toxicology, 2010; 100215135857018 DOI: 10.1021/tx900203v

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X-rays reveal uptake of nanoparticles by soybean crops

Date:

February 6, 2013

Source:

European Synchrotron Radiation Facility

Soya bean plants during their maturation in greenhouse conditions.

Credit: J.L. Gardea-Torresdey

Metals contained in nanoparticles can enter into the food chain. Scientists have, for the first time, traced the nanoparticles taken up from the soil by crop plants and analysed the chemical states of their metallic elements. Zinc was shown to dissolve and accumulate throughout the plants, whereas the element cerium did not dissolve into plant tissue. The results contribute to the controversial debate on plant toxicity of nanoparticles and whether engineered nanoparticles can enter into the food chain.---The study was published on 6 February 2013 in the journal ACS Nano.--The international research team was led by Jorge Gardea-Torresdey from the University of Texas in El Paso and also comprised scientists from the University of California in Santa Barbara, the SLAC National Accelerator Laboratory in Stanford (California), and the European Synchrotron Radiation Facility in Grenoble (France).---Nanoparticles are present everywhere, for example in the fine dust of wood fires. Even a simple chemical compound behaves differently as a nanoparticle, mostly due to the increased specific surface area and reactivity. These appealing properties are why so-called Engineered Nanoparticles (ENPs) are now widely used in industrial processing and consumer goods. At the same time, their high reactivity has raised concerns about their fate, transport and toxicity in the environment. "A growing number of products containing ENPs are in the market and eventually they will get into the soil, water and air. This is why it is very important to study the interactions of crops with nanoparticles, as their possible translocation into the food chain starts here." says Jorge Gardea-Torresdey, a Professor and Chair of the Department of Chemistry at the University of Texas at El Paso.---The scientists focused on soya bean plants (glycine max), the fifth largest crop in global agricultural production, and the second in the U.S. The soil in which the plants were grown was mixed with zinc oxide (ZnO) and cerium dioxide (CeO2, nanoceria) nanoparticles, which are among the most highly used in industry. ZnO is widely used in sunscreen products, as gas sensors, antibacterial agents, optical and electrical devices, and as pigments. Nanoceria is an excellent catalyst for internal combustion and oil cracking processes and is also used in gas sensors, sunscreen products and cosmetic creams.---After the soya bean plants had been grown to maturity in greenhouses, the distribution of zinc and cerium throughout the plants was studied. The use of microscopic synchrotron X-ray beams at the Stanford Synchrotron Radiation Lightsource (SSRL) and at the ESRF, enabled scientists to determine the chemical form of these metals, i.e. whether they were still bound to nanoparticles or had dissolved and bound with plant tissue. "We used X-ray beams 1000 times thinner than a human hair, and the way in which they are absorbed tells us whether, at the microscopic spot they hit, zinc and cerium were present, and whether they formed part of a nanoparticle in the plant or not." says Hiram Castillo, a scientist at the ESRF in Grenoble.--Cerium was shown to be present not only in the nodules close to the soil but had also reached the plant pods. A detailed spectral analysis of the X-ray signals showed that the cerium in the nodules and pods was in the same chemical state as in the nanoparticles. However, part of the cerium had changed its oxidation state from Ce(IV) to Ce(III) which can alter the chemical reactivity of the nanoparticles.---Zinc was detected in nodules, stems and pods in concentrations higher than in a control group of plants. The spectral analysis did not show the presence of zinc in the plants bound as ZnO nanoparticles which means that the zinc in the nanoparticles had been biotransformed. The spectra suggest that organic acids present in the plants such as citrate, are the probable ligands for the zinc.---"As zinc is present in most plants, it didn't come as a surprise that zinc from the nanoparticles in the soil can enter into the plant tissue. But plants can also assimilate more dangerous elements like cadmium or arsenic which, when used in nanoparticles, might pose a real threat." says Hiram Castillo. "Our results have also shown that CeO2 nanoparticles can be taken up by food crops when present in the soil. Cerium has no chemical partner in the plant tissue and is not biotransformed in the soya bean but still reaches the food chain and the next soya bean plant generation." adds Jorge Gardea-Torresdey.--"One must keep in mind that once engineered nanoparticles enter the food chain, this is an accumulative process. CTolerable levels today can become dangerous tomorrow.B This is why it is important to study not only whether man-made nanoparticles can be taken up from soil but also how they are biotransformed in the plants.[F10] " concludes Jorge Gardea-Torresdey.--Arturo A. Keller of the University of California in Santa Barbara and Co-Director of the UC Center for the Environmental Implications of Nanotechnology, who was not involved in this research, comments:

"It's a fascinating paper with some genuine concerns in terms of potential health implications. Whilst we are not able to directly attribute nanoparticle ingestion to any particular disease or symptoms, we know from the latest laboratory studies the potency some have in terms of infiltrating our cells and tissue and causing harm. The fact that these potentially dangerous particles are being taken up by such a common crop suggests a need to review what materials are used in agriculture around the world. In particular, it raises concern over the use of treated waste water to irrigate crops all over the world which may provide a route for these potentially dangerous particles to get into our bodies if the content of the water is not more tightly managed."[F11] ---Story Source-The above story is based on materials provided by European Synchrotron Radiation Facility. Note: Materials may be edited for content and length.--Journal Reference-Jose A. Hernandez-Viezcas, Hiram Castillo-Michel, Joy Cooke Andrews, Marine Cotte, Cyren Rico, Jose R. Peralta-Videa, Yuan Ge, John H. Priester, Patricia Ann Holden, Jorge L. Gardea-Torresdey. In SituSynchrotron X-ray Fluorescence Mapping and Speciation of CeO2and ZnO Nanoparticles in Soil Cultivated Soybean (Glycine max). ACS Nano, 2013; 130122094014001 DOI: 10.1021/nn305196q

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Nanoparticle thin films that self-assemble in one minute

Date:

June 9, 2014

Source:

DOE/Lawrence Berkeley National Laboratory

Upon solvent annealing, supramolecules made from gold nanoparticles and block copolymers will self-assemble into highly ordered thin films in one minute.--The days of self-assembling nanoparticles taking hours to form a film over a microscopic-sized wafer are over. Researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) have devised a technique whereby self-assembling nanoparticle arrays can form a highly ordered thin film over macroscopic distances in one minute.--Ting Xu, a polymer scientist with Berkeley Lab's Materials Sciences Division, led a study in which supramolecules based on block copolymers were combined with gold nanoparticles to create nanocomposites that under solvent annealing quickly self-assembled into hierarchically-structured thin films spanning an area of several square centimeters. The technique is compatible with current nanomanufacturing processes and has the potential to generate new families of optical coatings for applications in a wide number of areas including solar energy, nanoelectronics and computer memory storage. This technique could even open new avenues to the fabrication of metamaterials, artificial nanoconstructs that possess remarkable optical properties.--"Our technique can rapidly generate amazing nanoparticle assemblies over areas as large as a silicon wafer," says Xu, who also holds a joint appointment with the University of California (UC) Berkeley's Departments of Materials Sciences and Engineering, and Chemistry. "You can think of it as pancake batter that you can spread over a griddle, wait one minute and you have a pancake ready to eat."-Xu is the corresponding author of a paper describing this research in Nature Communications titled "Rapid fabrication of hierarchically structured supramolecular nanocomposite thin films in one minute." Co-authors are Joseph Kao, Kari Thorkelsson, Peter Bai, Zhen Zhang and Cheng Sun.--Nanoparticles function as artificial atoms with unique optical, electrical and mechanical properties. If nanoparticles can be induced to self-assemble into complex structures and hierarchical patterns, similar to what nature does with proteins, it would enable mass-production of devices a thousand times smaller those used in today's microtechnology.--Xu and her research group have been steadily advancing towards this ultimate goal. Most recently their focus has been on the use of block copolymer-based supramolecular solutions to direct the self-assembly of nanoparticle arrays. A supramolecule is a group of molecules that act as a single molecule able to perform a specific set of functions. Block copolymers are long sequences or "blocks" of one type of monomer bound to blocks of another type of monomer that have an innate ability to self-assemble into well-defined arrays of nano-sized structures over macroscopic distances.--"Block copolymer-based supramolecules self-assemble and form a wide range of morphologies that feature microdomains typically a few to tens of nanometers in size," Xu says. "As their size is comparable to that of nanoparticles, the microdomains of supramolecules provide an ideal structural framework for the self-assembly of nanoparticle arrays."--In the supramolecular technique devised by Xu and her colleagues, arrays of gold nanoparticles were incorporated into solutions of supramolecules to form films that were about 200 nanometers thick. Through solvent annealing, using chloroform as the solvent, the nanoparticle arrays organized into three-dimensional cylindrical microdomains that were packed into distorted hexagonal lattices in parallel orientation with the surface. This display of hierarchical structural control in nanoparticle self-assembly was impressive but was only half the game.--"To be compatible with nanomanufacturing processes, the self-assembly fabrication process must also be completed within a few minutes to minimize any degradation of nanoparticle properties caused by exposure to the processing environment," Xu says.--She and her group systematically analyzed the thermodynamics and kinetics of self-assembly in their supramolecular nanocomposite thin films upon exposure to solvent vapor. They found that by optimizing a single parameter, the amount of solvent, assembly kinetics could be precisely tailored to produce hierarchically structured thin films in a single minute.--"By constructing our block copolymer-based supramolecules from small molecules non-covalently attached to polymer side chains, we changed the energy landscape so that solvent content became the most important factor," Xu says. "This enabled us to achieve fast-ordering of the nanoparticle arrays with the addition of only a very small amount of solvent, about 30-percent of the fraction of a 200 nanometer thick film."--- The optical properties of nanocomposite thin films depend on the properties of individual nanoparticles and on well-defined inter-particle distances along different directions. Given that the dimensions of the gold nanoparticle arrays are at least one order of magnitude smaller than the wavelengths of visible light, the supramolecular technique of Xu and her colleagues has strong potential to be used for making metamaterials. These artificial materials have garnered a lot of attention in recent years because their electromagnetic properties are unattainable in natural materials. For example, a metamaterial can have a negative index of refraction, the ability to bend light backwards, unlike all materials found in nature, which bend light forward.-"Our gold nanocomposite thin films exhibit strong wavelength- dependent optical anisotropy that can be tailored simply by varying the solvent treatment," Xu says. "This presents a viable alternative to lithography for making metamaterials."--While Xu and her colleagues used gold nanoparticles in their films, the supramolecular approach is compatible with nanoparticles of other chemical compositions as well.--"We should be able to create a library of nanoparticle assemblies engineered for light manipulation and other properties," Xu says, "using a technique that is compatible with today's most widely used nanomanufacturing processes, including blade coating, ink-jet printing and dynamic zone annealing."--Story Source-The above story is based on materials provided by DOE/Lawrence Berkeley National Laboratory. The original article was written by Lynn Yarris. Note: Materials may be edited for content and length.-Journal Reference-Joseph Kao, Kari Thorkelsson, Peter Bai, Zhen Zhang, Cheng Sun, Ting Xu. Rapid fabrication of hierarchically structured supramolecular nanocomposite thin films in one minute. Nature Communications, 2014; 5 DOI: 10.1038/ncomms5053

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The Art of Self-Assembly

Nano-sized particles -- bits of matter a few billionths of a meter in size, or more than a hundred times smaller than the stuff of today's microtechnologies -- display highly coveted properties not found in macroscopic materials, including optical, electronic, magnetic, etc. The promise of nanotechnololgy is that exploiting these unique properties on a commercial scale could yield such "game-changers" as sustainable, clean and cheap energy, and the creation on demand of new materials with properties tailored to meet specific needs. Realizing this promise starts with nanoparticles being able to organize themselves into complex structures and hierarchical patterns, similar to what nature routinely accomplishes with proteins.--"Precise control of the spatial organization of nanoparticles and other nanoscopic building blocks over multiple length scales has been a bottleneck in the bottom-up generation of technologically important materials," says Xu. "Most of the approaches that have been used so far have involved surface modifications."--Small as they are, nanoparticles are essentially all surface so any process that modifies the surface of a nanoparticle can profoundly change the properties of that particle. Precisely arranging these nanoparticles is critical to tailoring the macroscopic properties during nanoparticle assembly. Although DNA has been used to induce self-assembly of nanoparticles with a high degree of precision, this approach only works well for organized arrays that are limited in size; it is impractical for large-scale fabrication. Xu believes a better approach is to use block copolymers -- long sequences or "blocks" of one type of monomer molecule bound to blocks of another type of monomer molecule.--"Block copolymers readily self-assemble into well-defined arrays of nanostructures over macroscopic distances," she says. "They would be an ideal platform for directing the assembly of nanoparticles except that block copolymers and nanoparticles are not particularly compatible with one another from a chemistry standpoint. A mediator is required to bring them together."--Xu and her group found such a "mediator" in the form of small molecules that will join with nanoparticles and then able attach themselves and their nanoparticle partners to the surface of a block copolymer. For this study, Xu and her group used two different types of small molecules, surfactants (wetting agents) dubbed "PDP" and "OPAP." These small molecules can be stimulated by light (PDP) or heat (OPAP) to sever their connection to the surface of a block copolymer and be repositioned to another location along the polymeric chain[F12] . In this manner, the spatial distribution of the small molecule mediators and their nanoparticle partners can be precisely directed with no need to modify either the nanoparticles or the polymers.--"The beauty of this technique is that it involves no sophisticated chemistry," says Xu. "It really is a plug and play technique, in which you simply mix the nanoparticles with the block copolymers and then add whatever small molecules you need."For this study, Xu and her colleagues added PDP or OPAP small molecules to various blends of nanoparticles, such as cadmium selenide and lead sulfide, mixed in with a commercial block copolymer -- polystyrene-block-poly (4-vinyl pyridine). While she and her group worked with light and heat, she says other stimuli, such as pH, could also be used to reposition small molecules and their nanoparticle partners along block copolymer formations. Strategic substitutions of different types of stimulus-responsive small molecules could serve as a mechanism for structural fine-tuning or for incorporating specific functional properties into nanocomposites. Xu and her colleagues are now in the process of adding functionality to their self-assembly technique.--"Bring together the right basic components -- nanoparticles, polymers and small molecules -- stimulate the mix with a combination of heat, light or some other factors, and these components will assemble into sophisticated structures or patterns," says Xu. "It is not dissimilar from how nature does it."--This research was supported in part by the U.S. Department of Energy's Office of Science and in part by the Army Research Office and National Science Foundation. The nanoparticles were synthesized at Berkley Lab's Molecular Foundry and characterizations of the nanoparticle assemblies were performed at Beamline 7.3.3 of Berkeley Lab's Advanced Light Source. Both the Molecular Foundry and the Advanced Light Source are DOE Office of Science national user facilities.--Story Source-The above story is based on materials provided by DOE/Lawrence Berkeley National Laboratory. Note: Materials may be edited for content and length.--Journal Reference-Ting Xu, Yue Zhao, Kari Thorkelsson, Alexander Mastroianni, Thomas Schilling, Joseph Luther, Benjamin Rancatore, Kazuyuki Matsunaga, Hiroshi Jinnai, Yue Wu, Daniel Poulsen, Jean Fréchet and Paul Alivisatos. Small molecule-directed nanoparticle assembly towards stimuli-responsive nanocomposites. Nature Materials, (in press)

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Synthetic and biological nanoparticles combined to produce new metamaterials 

December 19, 2012--Aalto University 

Scientists have succeeded in organizing virus particles, protein cages and nanoparticles into crystalline materials. These nanomaterials are important for applications in sensing, optics, electronics and drug delivery.

Two different protein cages, cowpea chlorotic mottle virus (blue) and Pyrococcus furiosus ferritin (red), can be used to guide the assembly of binary nanoparticles superlattices through tunable electrostatic interactions with charged gold nanoparticles (yellow).---

Scientists from Aalto University, Finland, have succeeded in organising virus particles, protein cages and nanoparticles into crystalline materials. These nanomaterials studied by the Finnish research group are important for applications in sensing, optics, electronics and drug delivery.-Layer structures, or superlattices, of crystalline nanoparticles have been extensively studied in recent years. The research develops hierarchically structured nanomaterials with tuneable optical, magnetic, electronic and catalytic properties. Such biohybrid superlattices of nanoparticles and proteins would allow the best features of both particle types to be combined. They would comprise the versatility of synthetic nanoparticles and the highly controlled assembly properties of biomolecules, according to the authors.-The research group also discovered magnetic self-assemblies of ferritin protein cages and gold nanoparticles. These magnetic assemblies can modulate efficiently spin-spin relaxation times of surrounding protons in water by enhancing the spin dephasing and consequently provide contrast enhancement in magnetic resonance imaging (MRI).-The gold nanoparticles and viruses adopt a special kind of crystal structure. It does not correspond to any known atomic or molecular crystal structure and it has previously not been observed with nano-sized particles.-Virus particles -- the old foes of humankind -- can do much more than infect living organisms. Evolution has rendered them with the capability of highly controlled self-assembly properties. Ultimately, by utilising their building blocks we can bring multiple functions to hybrid materials that consist of both living and synthetic matter, Kostiainen trusts.-

Youtube video link: http://youtu.be/lkkUe5xntNw

Story Source-The above story is based on materials provided by Aalto University. Note: Materials may be edited for content and length.--Journal Reference-Mauri A. Kostiainen, Panu Hiekkataipale, Ari Laiho, Vincent Lemieux, Jani Seitsonen, Janne Ruokolainen, Pierpaolo Ceci. Electrostatic assembly of binary nanoparticle superlattices using protein cages. Nature Nanotechnology, 2012; DOI: 10.1038/nnano.2012.220

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Lungs may suffer when certain elements go nano 2

Date:

January 27, 2014

Source:

Missouri University of Science and Technology--Nanoparticles are used in all kinds of applications -- electronics, medicine, cosmetics, even environmental clean-ups. More than 2,800 commercially available applications are now based on nanoparticles, and by 2017, the field is expected to bring in nearly $50 billion worldwide.--But this influx of nanotechnology is not without risks, say researchers at Missouri University of Science and Technology.--"There is an urgent need to investigate the potential impact of nanoparticles on health and the environment," says Yue-Wern Huang, professor of biological sciences at Missouri S&T.--Huang and his colleagues have been systematically studying the effects of transition metal oxide nanoparticles on human lung cells. These nanoparticles are used extensively in optical and recording devices, water purification systems, cosmetics and skin care products, and targeted drug delivery, among other applications.--"In their typical coarse powder form, the toxicity of these substances is not dramatic," says Huang. "But as nanoparticles with diameters of only 16-80 nanometers, the situation changes significantly."--The researchers exposed both healthy and cancerous human lung cells to nanoparticles composed of titanium, chromium, manganese, iron, nickel, copper and zinc compounds [F13] -- transition metal oxides that are on the fourth row of the periodic table. The researchers discovered that the nanoparticles' toxicity to the cells, or cytotoxicity, increased as they moved right on the periodic table.--"About 80 percent of the cells died in the presence of nanoparticles of copper oxide and zinc oxide," says Huang. "These nanoparticles penetrated the cells and destroyed their membranes. The toxic effects are related to the nanoparticles' surface electrical charge and available docking sites."--Huang says that certain nanoparticles released metal ions -- called ion dissolution -- which also played a significant role in cell death.--Huang is now working on new research that may help reduce nanoparticles' toxicity and shed light on how nanoparticles interact with cells.--"We are coating toxic zinc oxide nanoparticles with non-toxic nanoparticles to see if zinc oxide's toxicity can be reduced," Huang says. "We hope this can mitigate toxicity without compromising zinc oxide's intended applications. We're also investigating whether nanoparticles inhibit cell division and influence cell cycle."-The researchers' findings, "Cytotoxicity in the age of nano: The role of fourth period transition metal oxide nanoparticle physicochemical properties," were published in the Nov. 25, 2013, issue of the journal Chemico-Biological Interactions.--Story Source-The above story is based on materials provided by Missouri University of Science and Technology. Note: Materials may be edited for content and length.--Journal Reference-Yue-Wern Huang et al. Cytotoxicity in the age of nano: The role of fourth period transition metal oxide nanoparticle physicochemical properties. Chemico-Biological Interactions, January 2014

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Mesoporous silica nanoparticles inhibit cellular respiration.

Tao Z1, Morrow MP, Asefa T, Sharma KK, Duncan C, Anan A, Penefsky HS, Goodisman J, Souid AK.

Author information

Abstract

We studied the effect of two types of mesoporous silica nanoparticles, MCM-41 and SBA-15, on mitochondrial O 2 consumption (respiration) in HL-60 (myeloid) cells, Jurkat (lymphoid) cells, and isolated mitochondria. SBA-15 inhibited cellular respiration at 25-500 microg/mL; the inhibition was concentration-dependent and time-dependent. The cellular ATP profile paralleled that of respiration. MCM-41 had no noticeable effect on respiration rate. In cells depleted of metabolic fuels, 50 microg/mL SBA-15 delayed the onset of glucose-supported respiration by 12 min and 200 microg/mL SBA-15 by 34 min; MCM-41 also delayed the onset of glucose-supported respiration. Neither SBA-15 nor MCM-41 affected cellular glutathione. Both nanoparticles inhibited respiration of isolated mitochondria and submitochondrial particles

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Carbon black particle exhibits size dependent toxicity in human monocytes.

Sahu D1, Kannan GM1, Vijayaraghavan R2.

Author information

Abstract

Increased levels of particulate air pollution are associated with increased respiratory and cardiovascular mortality and morbidity. Some epidemiologic and toxicological researches suggest ultrafine particles (<100nm) to be more harmful per unit mass than larger particles. In the present study, the effect of particle size (nano and micro) of carbon black (CB) [F14] particle on viability, phagocytosis, cytokine induction, and DNA damage in human monocytes, THP-1 cells, was analysed. The cells were incubated with nanosize (~50nm) and micron (~500nm) size of CB particles in a concentration range of 50-800µg/mL. The parameters like MTT assay, phagocytosis assay, ELISA, gene expression, and DNA analysis were studied. Exposure to nano- and micron-sized CB particles showed size- and concentration dependent decrease in cell viability and significant increase in proinflammatory cytokines IL-1 β , TNF- α and IL-6 as well as chemokine IL-8 release. Gene expression study showed upregulation of monocyte chemoattractant protein-1 gene while cyclooxygenase-2 gene remained unaffected. Nano CB particles altered the phagocytic capacity of monocytes although micron CB had no significant effect. CB particles did not show any significant effect on DNA of monocytes. The investigations indicate that CB particles in nanosize exhibit higher propensity of inducing cytotoxicity, inflammation, and altered phagocytosis in human monocytes than their micron size.

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SBU-Led Study Reveals Nanoparticles Found in Everyday Items Can Inhibit Fat Storage Increase in gold nanoparticles can accelerate aging and wrinkling, slow wound healing, cause onset of diabetes

STONY BROOK, NY, April 18, 2013New research reveals that pure gold nanoparticles found in everyday items such as personal care products, as well as drug delivery, MRI contrast agents and solar cells can inhibit adipose (fat) storage and lead to accelerated aging and wrinkling, slowed wound healing and the onset of diabetes. The researchers, led by Tatsiana Mironava, a visiting assistant professor in the Department of Chemical and Molecular Engineering at Stony Brook University, detail their research, “Gold nanoparticles cellular toxicity and recovery: Adipose Derived Stromal cells,” in the journal Nanotoxicology.

Together with co-author Dr. Marcia Simon, Professor of Oral Biology and Pathology at Stony Brook University, and Director of the University’s Living Skin Bank, a world-class facility that has developed skin tissue for burn victims and various wound therapies, the researchers tested the impact of nanoparticles in vitro on multiple types of cells, including adipose (fat) tissue, to determine whether their basic functions were disrupted when exposed to very low doses of nanoparticles. Subcutaneous adipose tissue acts as insulation from heat and cold, functions as a reserve of nutrients, and is found around internal organs for padding, in yellow bone marrow and in breast tissue.---They discovered that the human adipose-derived stromal cells – a type of adult stem cells – were penetrated by the gold nanoparticles almost instantly and that the particles accumulated in the cells with no obvious pathway for elimination. The presence of the particles disrupted multiple cell functions, such as movement; replication (cell division); and collagen contraction; processes that are essential in wound healing.
[F15] --
According to the researchers, the most disturbing finding was that the particles interfered with genetic regulation, RNA expression and inhibited the ability to differentiate into mature adipocytes or fat cells. “Reductions caused by gold nanoparticles can result in systemic changes to the body,” said Professor Mironava. “Since they have been considered inert and essentially harmless, it was assumed that pure gold nanoparticles would also be safe. Evidence to the contrary is beginning to emerge.”
[F16]  -This study is also the first to demonstrate the impact of nanoparticles on adult stem cells, which are the cells our body uses for continual organ regeneration. It revealed that adipose derived stromal cells involved in regeneration of multiple organs, including skin, nerve, bone, and hair, ignored appropriate cues and failed to differentiate when exposed to nanoparticles. The presence of gold nanoparticles also reduced adiponectin, a protein involved in regulating glucose levels and fatty acid breakdown, which helps to regulate metabolism. ---
“We have learned that careful consideration and the choice of size, concentration and the duration of the clinical application of gold nanoparticles is warranted,” said Professor Mironava. “The good news is that when the nanoparticles were removed, normal functions were eventually restored.”-- 
“Nanotechnology is continuing to be at the cutting edge of science research and has opened new doors in energy and materials science,” said co-author, Miriam Rafailovich, PhD, Chief Scientist of the Advanced Energy Center and Distinguished Professor of Materials Science and Engineering at Stony Brook. “Progress comes with social responsibility and ensuring that new technologies are environmentally sustainable. These results are very relevant to achieving these goals.”--The research, funded by the National Science Foundation Materials Research Science and Engineering Centers (MRSEC) and Polymer Programs, was a collaboration of Stony
Brook University and New York State Stem Cell Science (NYSTEM). The paper was also co-authored by Michael Hadjiargyrou, Professor and Chairperson, Department of Life Sciences at New York Institute of Technology (NYIT) and former Professor in the Department of Biomedical Engineering at Stony Brook.

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Nanoparticles that look and act like cells

Date:

January 31, 2013

Source:

Methodist Hospital, Houston

Camouflaged nanoparticles (yellow) cloaked in the membranes of white blood cells rest on the surface of an immune system cell (phagocyte, blue) without being recognized, ingested, and destroyed.-[F17] -By cloaking nanoparticles in the membranes of white blood cells, scientists at The Methodist Hospital Research Institute may have found a way to prevent the body from recognizing and destroying them before they deliver their drug payloads.[F18]  The group describes its "LeukoLike Vectors," or LLVs, in a recent issue of Nature Nanotechnology.--"Our goal was to make a particle that is camouflaged within our bodies and escapes the surveillance of the immune system to reach its target undiscovered," Tasciotti said. "We accomplished this with the lipids and proteins present on the membrane of the very same cells of the immune system. We transferred the cell membranes to the surfaces of the particles and the result is that the body now recognizes these particles as its own and does not readily remove them."--Nanoparticles can deliver different types of drugs to specific cell types, for example, chemotherapy to cancer cells. But for all the benefits they offer and to get to where they need to go and deliver the needed drug, nanoparticles must somehow evade the body's immune system that recognizes them as intruders.[F19]  The ability of the body's defenses to destroy nanoparticles is a major barrier to the use of nanotechnology in medicine. Systemically administered nanoparticles are captured and removed from the body within few minutes. With the membrane coating, they can survive for hours unharmed[F20] .--"Our cloaking strategy prevents the binding of opsonins -- signaling proteins that activate the immune system," said Department of Medicine Co-Chair Ennio Tasciotti, Ph.D., the study's principal investigator. "We compared the absorption of proteins onto the surface of uncoated and coated particles to see how the particles might evade the immune system response."--Tasciotti and his group took metabolically active leukocytes (white blood cells) and developed a procedure to separate membranes from cell innards. By coating their nanoparticles with intact membranes in their native composition of lipids and proteins, the researchers created the first drug-carrying nanoparticles that look and act like cells -- leukolike vectors[F21] .--"Using the membranes of white blood cells to coat a nanoparticle has never been done before," Tasciotti said. "LLVs are half man-made -- the synthetic silicon core -- and half made of man -- the cell membrane."—

Can the membrane be produced entirely via synthetic means?

"Being able to use synthetic membranes or artificially-created membrane is definitely something we are planning for the future," Tasciotti said. "But for now, using our white blood cells is the most effective approach because they provide a finished product. The proteins that give us the greatest advantages are already within the membrane and we can use it as-is."--As the technology is developed, Tasciotti said a patient's own white cells could be harvested and used to create personalized LLVs. "Cloaked by the patient's own cell membranes, the nanoparticles would be far more likely to reach their targets and avoid the activation of the immune system surveillance," he said. To test whether the LLVs would be protected from macrophage sequestration and destruction, Tasciotti's team tested LLVs coated with human membranes and found that human macrophages left the LLVs unharmed, thus confirming the preservation of the self-recognition principle.--Nanoparticle research has generally focused on getting the particles to recognize specific tissue and to release drugs there, and only there. Comparative studies of LLVs' interaction with healthy and inflamed blood vessel cells showed the LLVs selectively targeted the inflamed tumor blood vessels.--"LLVs are dotted with proteins that help the particles reach specific targets, from inflamed or damaged tissues to cancer cells recruiting blood vessels," Tasciotti said. "Over time the membrane lipids and proteins will break away, leaving the nanoparticles to degrade naturally after releasing their payload."--The research team also looked at how well the drugs traveled through the LLV membrane. They found that rather than introducing an obstacle to drug release, the membrane provides controllable release of the drug once the nanoparticles reach their target tissue.[F22] --The present study used white blood cells from cell cultures. Tasciotti said one of his group's goals is culturing enough cells from the patient to be useful in drug therapy.--"We are aware that we will not always have access to an infinite number of white blood cells," Tasciotti said. "For this reason, we are working to optimize our system by using as little material as efficiently as possible. I expect this technology to become a new player in the crowded world of drug delivery system thanks to the opportunities it offers for the personalization of drug therapies."--Story Source-The above story is based on materials provided by Methodist Hospital, HoustonJournal Reference-Alessandro Parodi, Nicoletta Quattrocchi, Anne L. van de Ven, Ciro Chiappini, Michael Evangelopoulos, Jonathan O. Martinez, Brandon S. Brown, Sm Z. Khaled, Iman K. Yazdi, Maria Vittoria Enzo, Lucas Isenhart, Mauro Ferrari, Ennio Tasciotti. Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nature Nanotechnology, 2012; 8 (1): 61 DOI: 10.1038/nnano.2012.212

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In vitro phototoxicity and hazard identification of nano-scale titanium dioxide.

Sanders K1, Degn LL, Mundy WR, Zucker RM, Dreher K, Zhao B, Roberts JE, Boyes WK.

Author information

Abstract

Titanium dioxide nanoparticles (nano-TiO(2)) catalyze reactions under UV radiation and are hypothesized to cause phototoxicity. A human-derived line of retinal pigment epithelial cells (ARPE-19) was treated with six samples of nano-TiO(2) and exposed to UVA radiation. The TiO(2) nanoparticles were independently characterized to have mean primary particle sizes and crystal structures of 22nm anatase/rutile, 25nm anatase, 31nm anatase/rutile, 59nm anatase/rutile, 142nm anatase, and 214nm rutile. Particles were suspended in cell culture media, sonicated, and assessed for stability and aggregation by dynamic light scattering. Cells were treated with 0, 0.3, 1, 3, 10, 30, or 100μg/ml nano-TiO(2) in media for 24hrs and then exposed to UVA (2hrs, 7.53J/cm(2)) or kept in the dark. Viability was assessed 24hrs after the end of UVA exposure by microscopy with a live/dead assay (calcein-AM/propidium iodide). Exposure to higher concentrations of nano-TiO(2) with UVA lowered cell viability. The 25nm anatase and 31nm anatase/rutile were the most phototoxic (LC(50) with UVA<5μg/ml), while the 142nm anatase and 214nm rutile were the least phototoxic.[F23]  An acellular assay ranked TiO(2) nanoparticles for their UVA photocatalytic reactivities. The particles were found to be capable of generating thiobarbituric acid [F24] reactive substances (TBARS) under UVA. Flow cytometry showed that nano-TiO(2) combined with UVA decreased cell viability and increased the generation of reactive oxygen species (ROS, measured by Mitosox). LC(50) values under UVA were correlated with TBARS reactivity, particle size, and surface area.

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Protein Nanostructures
 
More research on the cytotoxicity of protein nanostructures is needed and proponents should weigh the risks
 carefully before introducing particles into foods, particularly on novel nanostructures, claim researchers- the
 review uses proteins as a case study to explore current knowledge and understanding of nanostructures in foods 
and the extent to which novel nanostructures may introduce new properties “Many of the foods we have been consuming
 for centuries already contain nanostructures, leading many to assume that they are safe. The extent to which novel 
nanostructures may afford new risks has not been adequately resolved, however, leading to concern within some consumer 
groups,” the researchers from Australia and New Zealand wrote However, despite the body evidence in support of nanostructures,
 the researchers said more thorough research is necessary to assess the of protein nanostructures 
Evidence has shown that even proteins not previously thought to be associated with disease can 
be toxic to cells and research suggests it is the intrinsic structural properties of food proteins that 
induce this toxicity, they said Nevertheless supporters of nanotechnology consider that there is plenty of evidence 
demonstrating the benign nature of the majority of protein nanostructures and instances where they may be harmful to
 humans are linked to specific protein sequences that can be managed Eliminating toxins It is possible to neutralise the toxicity 
of some nanoparticles using a heterogeneous mixtures of proteins, they said. For example, one study showed that the health risks
 associated with the homogeneous preparation of κ-casein is substantially lessened in a heterogeneous mixture containing β-casein 
The ability of β-casein to interact with a diversity of relatively hydrophobic proteins in a chaperone manner implies that it could be 
used in a broader contextAs a result, β-casein is now being considered as a nanovehicle to improve the solubility of curcumin, for 
example This example illustrates how the choice of protein and form of the nanostructure can determine whether a food component 
may be harmful or health promoting and that each case should be considered individually.” Far-reaching implications The researchers 
said the possible application of nanotechnology in food manufacturing and processing is far-reaching - to enhance food bioavailability
 and improve the colour, texture, flavour and safety properties For example, there are a range of new products currently on the market 
where ‘nanoparticles’ have been utilised to improve the release and delivery of dietary supplements and fat-soluble 
nutrients Other food proteins like lactoglobulin are being considered for their ability to alter food texture, gelling properties and 
digestibility, they said, and fungal proteins for their potential as surfactants; for example in the creation of air-filled emulsions in low
 fat ice-cream. Protein nanostructures in food – Should we be worried
 

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Self-assembled bionanostructures--proteins following the lead of DNA nanostructures

Natural polymers are able to self-assemble into versatile nanostructures based on the information encoded into their primary structure. The structural richness of biopolymer-based nanostructures depends on the information content of building blocks and the available biological machinery to assemble and decode polymers with a defined sequence. Natural polypeptides comprise 20 amino acids with very different properties in comparison to only 4 structurally similar nucleotides, building elements of nucleic acids. Nevertheless the ease of synthesizing polynucleotides with selected sequence and the ability to encode the nanostructural assembly based on the two specific nucleotide pairs underlay the development of techniques to self-assemble almost any selected three-dimensional nanostructure from polynucleotides. Despite more complex design rules, peptides were successfully used to assemble symmetric nanostructures, such as fibrils and spheres. While earlier designed protein-based nanostructures used linked natural oligomerizing domains, recent design of new oligomerizing interaction surfaces and introduction of the platform for topologically designed protein fold may enable polypeptide-based design to follow the track of DNA nanostructures. The advantages of protein-based nanostructures, such as the functional versatility and cost effective and sustainable production methods provide strong incentive for further development in this direction.

Keywords:

Self-assembly; Protein nanostructures-- DNA nanostructures; Protein origami

Introduction

The versatility of biopolymers can be used to rationally design new molecules and assemblies with structures and functionalities unseen in nature. The ability of biopolymers to self-assemble into complex shapes and structures defined at the nanometer scale, and our competence of sustainable large-scale production using cell factories makes them highly desirable for diverse technological applications. In the rapidly-growing research area of modern nanobiotechnology the natural components polypeptides and nucleic acids have been employed as building blocks for the assembling of new designed nanostructures and nanomaterials. Bionanotechnologists have in the last decades achieved important advances in protein-based and particularly DNA-based responsive nanostructures, which can now be designed to self-assemble into almost any selected shape.

Molecular self-assembly as the main organizing principle of biological systems is also a widely applied strategy in the nanotechnology as the driving force for the assembly of artificial nanostructures. In self-assembly the final structure is encoded by interactions of its building elements defined by their properties and the order of building blocks within the linear polymer. The shapes and functions of both, DNA- and protein-based nanostructures are encoded by the sequence of their constituents, nucleotides and amino acids. Additionally, the architecture of both type of the nanostructures can be affected also by the environmental factors, such as solvent, pH, temperature and building blocks concentration.

DNA nanostructures are based on the Watson-Crick nucleic base complementarity. There are only two different base pairs based on a specific pairwise interaction, where stacking with neighboring pairs underlies the formation of stable double-helical domains that serve as the nanostructural building blocks. Some of the most spectacular examples of the potentials of nanobiotechnology have been demonstrated by DNA-based nanostructures. In the nature the primary function of nucleic acids are the storage, processing and mediation of genetic information; however natural structures such as aptameres, telomeres and partially the ribosome as one of the key and most complex nanodevices are formed by nucleic acids assembled into 3D structures. The relevance of the physiological role of nucleic acids that perform their function in form of self-assembled noncoding RNA transcripts is still unknown. On the other hand artificial rationally designed DNA nanostructures, which utilize a narrower subset of interactions from aptameres, can adopt a huge diversity of 2D or 3D shapes [1-5].

In contrast to designed DNA nanostructures, the rational design of protein nanostructures is much more complicated due to the complex cooperative interactions between amino acids stabilizing the fold of native proteins. The comparison of some features of self-assembled DNA- and protein nanostructures is presented in Figure 1. Structural folding of most natural proteins still cannot be easily predicted from their primary structure due to contribution of many cooperative and long-range interactions between amino acids, therefore de novo design of completely new protein folds is even more challenging.

thumbnailFigure 1. Some features of self-assembled DNA- and protein nanostructures.

 Natural proteins comprise 20 amino acid residues with diverse properties in comparison to only 4 structurally similar nucleotides, building elements of nucleic acids. The advantages of protein nanostructures include also cheaper manufacturing of building blocks, as well as the multiple cooperative interactions that govering protein nanostructures.

However, a significant progress has been recently achieved in the development of strategies for building artificial self-assembled bionanostructures[F25] , and a range of both, DNA- and protein nanostructures rapidly increased in last two decades. In this review we mainly focus on protein-based nanostructure strategies, while DNA nanotechnology has been discussed in detail in many recent reviews [6-12].

Designed DNA nanostructures

In 1982, Seeman proposed to use DNA as the structural material for the bottom-up self-assembly [13] and he is accepted as the founder of the field of DNA nanotechnology. Since then, DNA-based self-assembly achieved spectacular results relying on the base-pairing specificity of nucleotides, using DNA synthesis technology, computer based design and, above all, imaginative design. Over the last three decades self-assembled DNA nanostructures have been extensively studied and several different approaches for building DNA nanostructures have been developed. Self-assembled DNA nanostructures range from 3D structures with a well-defined shape [2,4,14-17] to a variety of complex dynamic DNA devices [8,18-20]. This avenue of research also spawned DNA computing[F26]  [21,22] and design of dynamic devices [8,23,24], which are however beyond the scope of this review.

DNA self-assembly is a robust and flexible biomimetic strategy for molecular construction that is directed by the information embodied in the nucleotide sequence. Development of DNA nanostructures encompasses several different approaches (Figure 2), where the design of nanostructures is based on the assembly of:

– several medium-sized DNA (few 10–100 nucleotides) oligonucleotides that form finite sized nanostructures [14];

– several medium-sized DNA oligonucleotides that assemble into building blocks that further oligomerize into finite sized structures such as different polyhedra or into lattices [3,25];

– single long DNA scaffold (e.g. encompassing several 1000 nucleotides from the single stranded DNA phage) that is shaped into selected structure by the addition of short oligonucleotide clamps a.k.a. DNA origami technique, invented by Paul Rothemund [26]. This approach can result in complex 2D or 3D shapes such as molecular raster images, box, sphere etc.[F27]  [27-30];

– large number of short DNA bricks (32 or 42 nucleotide long strands that form U-shaped brick) that fill the 2D plane or 3D space, where the selected structure is formed by the omission of appropriate DNA bricks from the assembly mixture. Almost any 2D or 3D shape can be formed by this approach [15,31].

thumbnailFigure 2. Different approaches for building DNA nanostructures. The design of DNA nanostructure is based on the assembly of several medium-sized oligonucleotides that form either (a) a finite sized nanostructure or (b) assembled building blocks that further oligomerize into a finite sized nanostructure. (c) DNA nanostructure can be assembled from a single long DNA scaffold (blue) and short oligonucleotides (red, green) that hold the scaffold in place[F28] . (d) 2D and 3D nanostructures can be constructed by short DNA strands, DNA bricks.

An important advantage of DNA-based nanostructures is that it is possible to address the selected positions within the 2D or 3D nanostructures at approximately 5 nm resolution and introduce oligonucleotides with selected functionalities, such as different organic compounds, fluorophores, metal binding groups, proteins etc. into those positions, thereby functionalizing DNA nanostructures [F29] [9,32-36].

RNA has the distinct advantage that ssRNA could easily be produced in vivo in order to promote the self-assembly. This property was used to prepare RNA-based scaffolds with attached sites for functional proteins fused to specific sequence RNA binding domains. While those in vivo assembled structures were not well characterized, the scaffold strongly enhanced the reaction yield [37] similar to the DNA-based scaffolded enzymes, where the arrangement of enzymes had been linear [38]. It is hoped that this in vivo approach will be further developed for in vivo applications. ssDNA could also be produced in vivo, demonstrated by the self-assembly of a tetrahedron [39]. Isothermal DNA nanostructure assembly strategy has been developed that could further facilitate future DNA self-assembly in vivo [40].

DNA nanostructures were used to make devices that were functional in the cellular milieu; e.g. drug delivery container that encapsulates cargo, such as therapeutic antibodies, while opening of the container could be controlled by binding of the trigger signals to the aptamer lock that regulates opening of the container only if the triggering signals for both of the two locks are present [41]. DNA origami seems to be stable in vivo indicating that it is relatively protected against nucleases. There are also reports on the use of DNA nanostructures as the constituents of vaccines [42-44]. However real applications of DNA nanostructures are at the moment quite rare and essentially all DNA nanostructures are prepared by chemical synthesis, which limits the technological applications due to the cost and scale of production.

Protein nanostructures

Proteins provide masterful examples of complex self-assembling nanostructures with properties and functionalities beyond the reach of any human-made materials. It is estimated that there are only few thousand different protein folds in nature, and recently the number of new determined protein fold basically trickled to a halt despite determination of tens of thousands of new protein structures each year. So far folds of only few small protein domains can be accurately predicted [45-48] and design of completely new folds without resemblance to any of the existing native folds represents even a greater challenge [49].

Larger natural proteins have evolved through combinations of several smaller independently folding domains. Protein oligomerization based on the symmetric oligomerization domains is an important source of suprastructured proteins [50]. Existing protein oligomerization domains have been recognized as suitable building blocks for the predictable bottom-up design of artificial protein nanostructures. Strategies that used modified natural domains, or genetically or chemically linked secondary structure elements for self-assembling, and resulted in formation of symmetric intermolecular protein assemblies, lattices and heterogeneous cage-like assemblies, are described in reviews [51-53]. Recently we presented a new approach where a single polypeptide chain composed of concatenated coiled-coil-forming peptides self-assembled into a new topological fold, asymmetric tetrahedron-like cage, which is defined and stabilized by the specific pairing of the coiled-coil-forming segments arranged in a precisely defined order rather than cooperative packing of hydrophobic protein core [54].

Assemblies based on linked natural protein oligomerizing domains

The first strategy for the creation of designed protein nanostructures relied on interactions between oligomerizing[F30]  protein domains which typically comprise 100–200 or more amino acid residues. The domains can self-assemble non-covalently, but specifically into larger superstructures. Attempts in this direction have been pioneered with fusion strategy [55]. Two different oligomerizing domains, one promoting dimerization[F31]  and another one promoting homo-trimerization were linked by a semi-rigid linker (Figure 3a). Several copies of such a fusion protein were able to self-assemble into symmetric small cage-like but heterogeneous assemblies, or extended fibrils, depending on the length of the helical linker. Recent refinement of the original protein sequence resulted in a homogeneous 12-subunit assembly, confirmed by X-ray crystal structure determination. The structure of this oligomeric nanostructure reveals tetrahedral geometry with 16 nm diameter [56,57].

thumbnailFigure 3. Design strategies for symmetric domain-based intermolecular protein assemblies. (a) Fusion of natural oligomerizing protein domains. Two different oligomeric protein domains (dimerization domain (pink), trimerization domain (blue)) are genetically fused via helical linker (violet) to obtain a single chain building block which self-assembled into a 12-subunit cage-like structure with tetrahedral shape (4d9j) [56]. (b) Novel protein domain interface design. Computational design of additional interaction surfaces (red) on natural trimerization domain (blue) leads to the formation of 12-subunit assembly with tetrahedral - or 24-subunit assembly with octahedral symmetry (4ddf) [62].

This approach provides the possibility to create smart bionanomaterials by regulating the assembly and disassembly. Self-assembly of the fusion protein composed of the dimerizing gyrase B domain and trimerization domain can be driven by the addition of a small molecule. The addition of pseudo-dimeric gyrase B ligand, coumermycin, induced formation of hexagonal assemblies and its dissociation by the subsequent addition of a monomeric ligand novobiocin, which competes for binding to the same gyrase B site as the pseudodimeric coumermycin [58].

The extended fusion strategy circumvented the problem of connecting two oligomerization domains in a fixed relative orientation which assured well-ordered self-assembled protein nanostructures [59]. They showed that fusion protein can be made by selecting two or more connections between the adjacent oligomers if the two domains are joined along an axis of symmetry that both oligomerization domains share. However this symmetry-matching fusion protein strategy successfully manufactured linear filaments, two-dimensional lattices and large solid aggregates, but is not suitable for designing defined cage-like structures.

Engineering new interaction surfaces into native protein domains

In the strategies described above the range of suitable protein domains is limited by restrictions regarding the symmetry axes of the natural domains. A step further towards the design of artificial protein nanostructures was done by engineering domain surfaces for weak non-covalent interactions in the self-assembling processes. The analysis of natural contact interfaces between protein domains disclosed the rules governing domain association. The contacting surfaces should be complementary and predominantly non-polar. The contribution of hydrogen bonds and salt bridges at the contact rim is negligible. Employing these rules it was demonstrated that a given protein can be engineered to form new contact interfaces that produced a number of novel assemblies [60]. Algorithm Rosetta for modeling protein-protein interactions [61] enables de novo design of interacting interfaces which can drive the self-assembly of designed proteins into a desired symmetric architecture [46,62]. In a recent study, a computational design of protein nanostructures with atomic level accuracy was described [62]. Protein building blocks, based on natural trimeric protein domains were docked together symmetrically to the target packing arrangements and low-energy protein-protein interaction interfaces were designed between building blocks in order to drive the self-assembly (Figure 3b). The designed proteins assembled into cage-like nanostructures with either tetrahedral or octahedral point group symmetry which was confirmed by crystal structures.

Modular approach for de novo designed protein nanostructures

The strategies employing oligomerizing protein domains for designing new protein structures, described above, are limited to homologues of known native protein folds. The next generation engineering approaches are based on modules that can be considerably smaller than the typical protein domain. The modules comprise interacting de novo designed secondary structure elements that are predictably combined with specified partners to form larger assemblies. De novo protein design refers to attempts to construct completely new protein sequences for the prescribed structures based on the principles defining the stability and selectivity of building modules; in de novo design the polypeptide sequence is selected by the designer.

Modularity and orthogonality are two foundation concepts of de novo design and engineering of new protein nanostructures. Instead of optimization of the numerous cooperative interactions that underpin the structures of natural proteins, the use of well-understood structural modules, which could be combined into complex nanostructures, was proposed. α-helices and β-strands represent attractive protein folding motifs to serve as building blocks for well-ordered and defined nanostructures with complex architecture [63-67].

The most studied module for building self-assembled protein nanostructures are interacting helical peptides and particularly coiled-coils. They are ubiquitous facilitators of inter- and intramolecular protein-protein interactions and comprise two or more intertwined α-helices that are encoded by the characteristic heptad sequence repeat, where residues are labeled with abcdefg. The non-covalent interactions that drive the formation of coiled-coils are the hydrophobic effects between amino acids at positions a and d that form a hydrophobic core of coiled-coil, and the electrostatic inteactions between the opposite charged residues at positions e and g. The rules governing coiled-coil formation, their oligomerization state and interaction partner specificity have been considerably established over the last decades [68,69]. On the basis of those rules sets of orthogonal designed coiled-coils as the toolkit for the designed protein assemblies were developed [70-75]. Engineered coiled-coil polypeptides have been used to assemble different nanomaterials: nanofibres [76,77], membranes [78], nanotubes [79], nanostructured films [80], spherical structures [81], responsive hydrogels [82,83], spheres [84] etc. Homogeneous nanoparticles with regular polyhedral symmetry, about 16 nm in diameter, were prepared from single type of polypeptide chains where the two coiled-coil modules with different oligomerization states were joined by a short linker [85]. In another study two oligomerizing coiled-coil peptides were tethered via disulphide bond close to their center. The self-assembled molecules spontaneously curved into the spherical cage-like particles, with a hexagonal-pattern of the cage surface and about 100 nm in diameter [84]. Another example are discrete circular nanostructures of defined stoichiometry; trimers or tetramers of < 10 nm were observed when linker between two coiled-coil-forming segments comprising 6–10 residues. Larger colloidal-scale assemblies as well as flexible fibers were formed when shorter linkers limited flexibility between peptides [86].

Designed topological protein folds based on interacting coiled-coil modules

Recent innovative approach to construct new engineered self-assembled protein nanostructures is based on the concatenated interacting dimerizing modules, comprise up to 45 amino acid residues [54]. The tetrahedral nanostructure was built from only single polypeptide chain; this strategy may appropriately be called designed protein origami as opposed to native protein structures that fold into a defined 3D structure from a single chain.

Rather than folding the structure based on the interactions between residues in the hydrophobic core as for the native proteins, the modular topological design is based on pairwise interactions between concatenated secondary structure elements (coiled-coil-forming segments), whose folding and orthogonality is engineered independently. Orthogonality of used coiled-coil building modules ensures that each segment preferentially binds to its designated partner segment within the same polypeptide chain. The final topology is defined by the sequential order of coiled-coil segments. The topological fold comprises a cavity bounded by coiled-coil dimers as the edges of the polyhedron. This type of modular self-assembly therefore in many aspects resembles the principles of DNA nanostructures [2,3,26], where polyhedra had been constructed based on the complementary DNA segments.

According to this approach long range non-covalent interactions occur between coiled-coil-forming segments, which dimerize independently of the other segments. The coiled-coil-forming segments are concatenated into a precisely defined order with intervening flexible linkers between each segment, to provide the hinge-like flexibility. In the case of a monomeric tetrahedron, which was constructed to demonstrate the principle, the polypeptide chain is composed of 12 designed coiled-coil dimer- forming segments, each forming an orthogonal coiled-coil dimer with its partner segment within the same polypeptide chain (Figure 4). In this way it forms 6 edges of a tetrahedron, while the flexible linkers were positioned at vertices. The polypeptide was produced in the recombinant form in E. coli and self-assembled by a slow dialysis or temperature annealing into tetrahedral structure, whose edges measure around 5 nm. This direction opens an exciting perspective for the creation of additional entirely new protein folds. The principle of protein assembly can benefit significantly by the application of a mathematical topology theory, which can be used to analyze the number of theoretical solutions and may be in the future applied to optimize the kinetics of the assembly [87]. The results of protein nanocage engineering show that modular design can be used for complex structures, with the potential for applications biocatalysis, targeted drug delivery, vaccination, etc. [88].

thumbnailFigure 4. Protein origami: modular topological design of protein structure from a single polypeptide chain. A toolbox for constructing tetrahedron-like cage comprised of six orthogonal pairs of coiled-coil-forming peptides, two antiparallel- and four parallel dimers (orientation is denoted by arrow). Twelve peptides were concatenated in a defined order, separated by the tetrapeptide linker. The single polypeptide chain served as a building block that self-assembled into monomeric and asymmetric tetrahedron-like nanostructure [54].

Conclusions and future prospects

The recent successes in the design of new bionanostructures based on DNA and protein demonstrates the potentials of this approach to engineer new functional nanostructures.

While DNA-based nanostructures are clearly ahead of the designed protein nanostructures in terms of the complexity of the designed structures so far they lacked tangible applications. Although it has been demonstrated that DNA-based nanostructures are functional in organisms, use of in vivo produced and assembled nucleic acid-based nanostructures would represent an important step ahead both for the production cost and new biological applications. Functionalization of nucleic acids could combine structural design with precisely addressed functionalities. However, proteins adopt much larger conformational variability than nucleic acids and provide more versatile functionality. De novo design of protein nanostructures has been limited to small number of application cases which predominatly utilizing repurposed natural protein domains. Nevertheless the design of protein assemblies has matured beyond the proof of principles and is ready to face more complex challenges. New emerging paradigms such as the topological protein folds open completely new avenues that seem not to have been adopted or perhaps even tested by nature. Future developments will demonstrate the potentials of different strategies, or their combinations, with respect to the precise engineering of nanostructures and the theoretical limitations of different platforms. The next stage will need to focus on application development. The potentials are numerous, from targeted drug and biomolecule delivery, vaccine design, tissue engineering, senzors design, biocatalysis to bionanomaterials science. The interdisciplinary approach of synthetic biology, combining structural biology, molecular biology,[F32]  mathematics, engineering and many other disciplines, have the potential to join forces in this exciting opportunity.

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Polymerization

In each other's presence, the different types of amino acid molecules undergo chemical reactions that make them bond together and form larger molecules. Scientists refer to molecules that go through these accumulating reactions as monomers. Since they come from chains of monomers, proteins are also known as polymers. To qualify as proteins, amino acid chains must contain more than about 30 individual acids. If roughly 30 or fewer amino acids bond together, the resulting chains are typically referred to as peptides.

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DNA-linked nanoparticles form switchable 'thin films' on a liquid surface

Date:

June 11, 2014

Source:

Brookhaven National Laboratory

Schematic illustration of the assembly of DNA-functionalized nanoparticles (NPs) at positively charged interfaces. (a) In the absence of salt, ...

[show more]

 Image courtesy of Brookhaven National Laboratory

Scientists seeking ways to engineer the assembly of tiny particles measuring just billionths of a meter have achieved a new first -- the formation of a single layer of nanoparticles on a liquid surface where the properties of the layer can be easily switched. Understanding the assembly of such nanostructured thin films could lead to the design of new kinds of filters or membranes with a variable mechanical response for a wide range of applications. In addition, because the scientists used tiny synthetic strands of DNA to hold the nanoparticles together[F33] , the study also offers insight into the mechanism of interactions of nanoparticles and DNA molecules near a lipid membrane. This understanding could inform the emerging use of nanoparticles as vehicles for delivering genes across cellular membranes.

"Our work reveals how DNA-coated nanoparticles interact and re-organize at a lipid interface, and how that process affects the properties of a "thin film" made of DNA-linked nanoparticles," said physicist Oleg Gang who led the study at the Center for Functional Nanomaterials (CFN) at the U.S. Department of Energy's Brookhaven National Laboratory. The results will be published in the June 11, 2014 print edition of the Journal of the American Chemical Society.

Like the molecule that carries genetic information in living things, the synthetic DNA strands used as "glue" to bind nanoparticles in this study have a natural tendency to pair up when the bases that make up the rungs of the twisted-ladder shaped molecule match up in a particular way. Scientists at Brookhaven have made great use of the specificity of this attractive force to get nanoparticles coated with single synthetic DNA strands to pair up and assemble in a variety of three-dimensional architectures. The goal of the present study was to see if the same approach could be used to achieve designs of two-dimensional, one-particle-thick films.

"Many of the applications we envision for nanoparticles, such as optical coatings and photovoltaic and magnetic storage devices, require planar geometry," said Sunita Srivastava, a Stony Brook University postdoctoral researcher and the lead author on the paper. Other groups of scientists have assembled such planes of nanoparticles, essentially floating them on a liquid surface, but these single-layer arrays have all been static, she explained. "Using DNA linker molecules gives us a way to control the interactions between the nanoparticles[F34] ."

As described in the paper, the scientists demonstrated their ability to achieve differently structured monolayers, from a viscous fluid-like array to a more tightly woven cross-linked elastic mesh -- and switch between those different states -- by varying the strength of the pairing between complementary DNA strands and adjusting other variables, including the electrostatic charge [F35] on the liquid assembly surface and the concentration of salt.

When the surface they used, a lipid, has a strong positive charge it attracts the negatively charged DNA strands that coat the nanoparticles. That electrostatic attraction and the repulsion between the negatively charged DNA molecules surrounding adjacent nanoparticles overpower the attractive force between complementary DNA bases. As a result, the particles form a rather loosely arrayed free-floating viscous monolayer. Adding salt changes the interactions and overcomes the repulsion between like-charged DNA strands, allowing the base pairs to match up and link the nanoparticles together more closely, first forming string-like arrays, and with more salt, a more solid yet elastic mesh-like layer.

"The mechanism of this phase transition is not obvious," said Gang. "It cannot be understood from the repulsion-attraction interactions alone. With the help of theory, we reveal that there are collective effects of the flexible DNA chains that drive the system in the particular states. And it is only possible when the particle sizes and the DNA chain sizes are comparable -- on the order of 20-50 nanometers," he said.

[F36] As part of the study, the scientists examined the different configurations of the nanoparticles on top of the liquid layer using x-ray scattering at Brookhaven's National Synchrotron Light Source (NSLS). They also transferred the monolayer produced at each salt concentration to a solid surface so they could visualize it using electron microscopy at the CFN.

"Creating these particle monolayers at a liquid interface is very convenient and effective because the particles' two-dimensional structure is very 'fluid' and can be easily manipulated -- unlike on a solid substrate, where the particles can easily get stuck to the surface," Gang said. "But in some applications, we may need to transfer the assembled layer to such a solid surface. By combining the synchrotron scattering and electron microscopy imaging we could confirm that the transfer can be done with minimal disruption to the monolayer."

The switchable nature of the monolayers might be particularly attractive for applications such as membranes used for purification and separations, or to control the transport of molecular or nano-scale objects through liquid interfaces. For example, said Gang, when particles are linked but move freely at the interface, they may allow an object -- a molecule -- to pass through the interface. "However, when we induce linkages between particles to form a mesh-like network, any object larger than the mesh-size of the network cannot penetrate through this very thin film. "

"In principle, we can even think about such on-demand regulated networks to adjust the mesh size dynamically. Because, of the nanoscale size-regime, we might envision using such membranes for filtering proteins or other nanoparticles," he said.

Understanding how synthetic DNA-coated nanoparticles interact with a lipid surface may also offer insight into how such particles coated with actual genes might interact with cell membranes -- which are largely composed of lipids -- and with one another in a lipid environment.

"Other groups have considered using DNA-coated nanoparticles to detect genes within cells, or even for delivering genes to cells for gene therapy and such approaches[F37] ," said Gang. "Our study is the first of its kind to look at the structural aspects of DNA-particle/lipid interface directly using x-ray scattering. I believe this approach has significant value as a platform for more detailed investigations of realistic systems important for these new biomedical applications of DNA-nanoparticle pairings," Gang said.

This research was sponsored by the DOE Office of Science.

Story Source-The above story is based on materials provided by Brookhaven National Laboratory. Note: Materials may be edited for content and length.

Journal Reference-Sunita Srivastava, Dmytro Nykypanchuk, Masafumi Fukuto, Jonathan D. Halverson, Alexei V. Tkachenko, Kevin G. Yager, Oleg Gang. Two-Dimensional DNA-Programmable Assembly of Nanoparticles at Liquid Interfaces. Journal of the American Chemical Society, 2014; 136 (23): 8323 DOI: 10.1021/ja501749b

 


 [F1]Silver Nano Particles

 [F2]Which in the nano form form lattices and can be mixed with proteins and metals and a assortment of chemicals that could not be combined or contained without this technology and with this tech wil produce things that the systems cane be completely over run or changed permenantly

 [F3]Morphing the materials to form a different type of material but on a nano scale and the density would also change as well as the means of degradation

 [F4]Making  a chemical reaction more effective or efficient-and has multiple environmental applications

 [F5]The key here would be to break the bound or ligand to separate the ripening of these components

 [F6]Interesting play on words it is not saying straight out but it is still harmful ---just not as bad  as the other

 [F7]Interestingly when copper and zinc combine normally they produce SOD which benefits the body here

 [F8]Human Cell Carcinoma Line---so it was not just the mouse but a Human Cell

 [F9]So your now getting it in the food supply as well since this does not wash off

 [F10]And then when human consumption is occurring how they biotransform us as well this would be a carry over into or DNA andn Genetic structure

 

 [F11]Nano Particles are in chemtrails and when it rains there might ne good cause to assume these particles are in this synthetic rain

 [F12]Morpholgy—the adjusting or restructuring of a polymr

 [F13]Which interestingly enough also are in chemtrails

 [F14]Carbon black is a form of paracrystalline carbon that has a high surface-area-to-volume ratio, albeit lower than that of activated carbon. It is dissimilar to soot in its much higher surface-area-to-volume ratio and significantly lower (negligible and non-bioavailable

Material produced by the incomplete combustion of heavy petroleum products such as FCC tar, coal tar, ethylene cracking tar, and a small amount from vegetable oil.

 [F15]Normally Gold assist in the regeneration of the body but in a nano format it would appear it does the opposite and this could be because the amount so small and so much concentrates in the cells or tissues that it actually creates a metal overload which the body isunable to resolve due to the concentration and permeation of those areas

 [F16]And not just in Gold ---almost all nano metals or minerals when in this scale seem to cause systemic changes and immune system –imepdiments or shut down that would normally occur

 [F17]This is alarming when You se the implications here ---with an injection-consumption or a topical you could literally cause a complete re write of the immune system  or organ function ---making a condition to rapidly cause  a cascading of the bio system ---if the immune system cannot recognize this then what happens isa hijacking of DNA –Chromosoms-or Genetics will occur

 [F18]Payload is a good description –the question is of what---if a drug today in the pharma business can cause 30 unwanted side effects---what happens inthis scenario since anything on a nano scale behaves entirely differently and can be rogue in the effect it has?

 

 [F19]Morgellons is a bio/polymer nano that is not recognized by the immune system and hijacks the DNA

 [F20]Again this is at best hypothetical since on a nano scale nothing is the same and if the camoflauge is successful enough ---could go undetected and accumulate causing  cellular and immune cascading

 [F21]Pay attention Here-- leukolike vectors [F21]-"LLVs are half man-made -- the synthetic silicon core -- and half made of man -- the cell membrane."—

 

So the idea that they will last for a few hours is not accurate---the drug that is being delivered may last a few hours but the delivery mechanism –may withstand for an indefinite period of time

 [F22]Controllable release of drug---what about biowarfare??

 [F23]Does not mean safe at all just means it was not as lethal

 [F24]Thiobarbituric acid reactive substances - TBARS - are formed as a byproduct of lipid peroxidation (i.e. as degradation products of fats) which can be detected by the TBARS assay using thiobarbituric acid as a reagent.

 [F25]Self Assembled BIO Nano structures

 [F26]Sounds Like A self contained program –or an AI

 [F27]This can be the morgellons---this is how morgellons replicates in us

 [F28]This is what will come out as a coloured crystal or scaffold proteins when they release from the cells or tissues

 [F29]This is where the overwrite can occur---when the program is sequenced and then targeted ---it will immediately utilize the proteins in the body or fat or any type of sugar( cellulose fibres to forma ligand bond) to further it’s replication process

 [F30]oligomer (plural oligomers)
  1. (chemistry) A compound intermediate between a monomer and a polymer, normally having a specified number of units between about five and a hundred.

 [F31]A dimer (/ˈdaɪmər/) (di-, "two" + -mer, "parts") is an oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular.

 [F32]Here in lies the problem---where does one begin and the other end where does the synthetic start and the natural become lost in the intertwining—what is happening here is a new form of life with proteins and nonproteins synthesized—and there is absolutely no way of knowing how this will interact with human-animal-or plant based DNA---the structure could literally repopulate the species with a whole new set of everything

 [F33]If you read here tiny synthetic strands of DNA ---this should be raising an eye brow and the fact that they can interface with fats

 [F34]And this can be done in any environment—in people and animals and plants—fish and insects as well

 [F35]Using an electrical stimuli--- When two objects in each other's vicinity have different electrical charges, an electrostatic field exists between them. An electrostatic field also forms around any single object that is electrically charged with respect to its environment. An object is negatively charged (-) if it has an excess of electrons relative to its surroundings. An object is positively charged (+) if it is deficient in electrons with respect to its surroundings.

Electrostatic fields bear some similarity to magnetic  fields. Objects attract if their charges are of opposite polarity (+/-);objects repel if their charges are of the same polarity (+/+ or -/-). The lines of electrostatic flux in the vicinity of a pair of oppositely charged objects are similar to lines of magnetic flux between and around a pair of opposite magnetic poles. In other ways, electrostatic and magnetic fields differ. Electrostatic fields are blocked by metallic objects, while magnetic fields can pass through most (but not all) metals. Electrostatic fields arise from a potential difference or voltage gradient, and can exist when charge carriers, such as electrons, are stationary (hence the "static"in "electrostatic"). Magnetic fields arise from the movement of charge carriers, that is, from the flow of current.

When charge carriers are accelerated (as opposed to moving at constant velocity), a fluctuating magnetic field is produced. This gives rise to a fluctuating electric field, which in turn produces another varying magnetic field. The result is a "leapfrog" effect, in which both fields can propagate over vast distances through space. Such a synergistic field is known as an electromagnetic field, and is the phenomenon that makes wireless communications, broadcasting, and control systems possible. 

 [F36]Which can penetrate the skin

 [F37]What is a Gene? Genes are a set of instructions that determine what the organism is like, its appearance, how it survives, and how it behaves in its environment.--
The genes lie in long strands of DNA (deoxyribonucleic acid) called chromosomes.

 

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