Tag Archives: gold nanoparticles

Nanotechnology, tobacco plants, and the Ebola virus

Before presenting information about the current Ebola crisis and issues with vaccines and curatives, here’s a description of the disease from its Wikipedia entry,

Ebola virus disease (EVD) or Ebola hemorrhagic fever (EHF) is a disease of humans and other primates caused by an ebola virus. Symptoms start two days to three weeks after contracting the virus, with a fever, sore throat, muscle pain, and headaches. Typically nausea, vomiting, and diarrhea follow, along with decreased functioning of the liver and kidneys. Around this time, affected people may begin to bleed both within the body and externally. [1]

As for the current crisis in countries situated on the west coast of the African continent, there’s this from an Aug. 14, 2014 news item on ScienceDaily,

The outbreak of Ebola virus disease that has claimed more than 1,000 lives in West Africa this year poses a serious, ongoing threat to that region: the spread to capital cities and Nigeria — Africa’s most populous nation — presents new challenges for healthcare professionals. The situation has garnered significant attention and fear around the world, but proven public health measures and sharpened clinical vigilance will contain the epidemic and thwart a global spread, according to a new commentary by Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Dr. Fauci’s Aug. 13, 2014 commentary (open access) in the New England Journal of Medicine provides more detail (Note: A link has been removed),

An outbreak of Ebola virus disease (EVD) has jolted West Africa, claiming more than 1000 lives since the virus emerged in Guinea in early 2014 (see figure) Ebola Virus Cases and Deaths in West Africa (Guinea, Liberia, Nigeria, and Sierra Leone), as of August 11, 2014 (Panel A), and Over Time (Panel B).). The rapidly increasing numbers of cases in the African countries of Guinea, Liberia, and Sierra Leone have had public health authorities on high alert throughout the spring and summer. More recent events including the spread of EVD to Nigeria (Africa’s most populous country) and the recent evacuation to the United States of two American health care workers with EVD have captivated the world’s attention and concern. Health professionals and the general public are struggling to comprehend these unfolding dynamics and to separate misinformation and speculation from truth.

In early 2014, EVD emerged in a remote region of Guinea near its borders with Sierra Leone and Liberia. Since then, the epidemic has grown dramatically, fueled by several factors. First, Guinea, Sierra Leone, and Liberia are resource-poor countries already coping with major health challenges, such as malaria and other endemic diseases, some of which may be confused with EVD. Next, their borders are porous, and movement between countries is constant. Health care infrastructure is inadequate, and health workers and essential supplies including personal protective equipment are scarce. Traditional practices, such as bathing of corpses before burial, have facilitated transmission. The epidemic has spread to cities, which complicates tracing of contacts. Finally, decades of conflict have left the populations distrustful of governing officials and authority figures such as health professionals. Add to these problems a rapidly spreading virus with a high mortality rate, and the scope of the challenge becomes clear.

Although the regional threat of Ebola in West Africa looms large, the chance that the virus will establish a foothold in the United States or another high-resource country remains extremely small. Although global air transit could, and most likely will, allow an infected, asymptomatic person to board a plane and unknowingly carry Ebola virus to a higher-income country, containment should be readily achievable. Hospitals in such countries generally have excellent capacity to isolate persons with suspected cases and to care for them safely should they become ill. Public health authorities have the resources and training necessary to trace and monitor contacts. Protocols exist for the appropriate handling of corpses and disposal of biohazardous materials. In addition, characteristics of the virus itself limit its spread. Numerous studies indicate that direct contact with infected bodily fluids — usually feces, vomit, or blood — is necessary for transmission and that the virus is not transmitted from person to person through the air or by casual contact. Isolation procedures have been clearly outlined by the Centers for Disease Control and Prevention (CDC). A high index of suspicion, proper infection-control practices, and epidemiologic investigations should quickly limit the spread of the virus.

Fauci’s article makes it clear that public concerns are rising in the US and I imagine that’s true of Canada too and many other parts of the world, not to mention the countries currently experiencing the EVD outbreak. In the midst of all this comes a US Food and Drug Administration (FDA) warning as per an Aug. 15, 2014 news item (originated by Reuters reporter Toni Clarke) on Nanowerk,

The U.S. Food and Drug Administration said on Thursday [Aug. 14, 2014] it has become aware of products being sold online that fraudulently claim to prevent or treat Ebola.

The FDA’s warning comes on the heels of comments by Nigeria’s top health official, Onyebuchi Chukwu, who reportedly said earlier Thursday [Aug. 14, 2014] that eight Ebola patients in Lagos, the country’s capital, will receive an experimental treatment containing nano-silver.

Erica Jefferson, a spokeswoman for the FDA, said she could not provide any information about the product referenced by the Nigerians.

The Aug. 14,  2014 FDA warning reads in part,

The U.S. Food and Drug Administration is advising consumers to be aware of products sold online claiming to prevent or treat the Ebola virus. Since the outbreak of the Ebola virus in West Africa, the FDA has seen and received consumer complaints about a variety of products claiming to either prevent the Ebola virus or treat the infection.

There are currently no FDA-approved vaccines or drugs to prevent or treat Ebola. Although there are experimental Ebola vaccines and treatments under development, these investigational products are in the early stages of product development, have not yet been fully tested for safety or effectiveness, and the supply is very limited. There are no approved vaccines, drugs, or investigational products specifically for Ebola available for purchase on the Internet. By law, dietary supplements cannot claim to prevent or cure disease.

As per the FDA’s reference to experimental vaccines, an Aug. 6, 2014 article by Caroline Chen, Mark Niquette, Mark Langreth, and Marie French for Bloomberg describes the ZMapp vaccine/treatment (Note: Links have been removed),

On a small plot of land incongruously tucked amid a Kentucky industrial park sit five weather-beaten greenhouses. At the site, tobacco plants contain one of the most promising hopes for developing an effective treatment for the deadly Ebola virus.

The plants contain designer antibodies developed by San Diego-based Mapp Biopharmaceutical Inc. and are grown in Kentucky by a unit of Reynolds American Inc. Two stricken U.S. health workers received an experimental treatment containing the antibodies in Liberia last week. Since receiving doses of the drug, both patients’ conditions have improved.

Tobacco plant-derived medicines, which are also being developed by a company whose investors include Philip Morris International Inc., are part of a handful of cutting edge plant-based treatments that are in the works for everything from pandemic flu to rabies using plants such as lettuce, carrots and even duckweed. While the technique has existed for years, the treatments have only recently begun to reach the marketplace.

Researchers try to identify the best antibodies in the lab, before testing them on mice, then eventually on monkeys. Mapp’s experimental drug, dubbed ZMapp, has three antibodies, which work together to alert the immune system and neutralize the Ebola virus, she [Erica Ollman Saphire, a molecular biologist at the Scripps Research Institute,] said.

This is where the tobacco comes in: the plants are used as hosts to grow large amounts of the antibodies. Genes for the desired antibodies are fused to genes for a natural tobacco virus, Charles Arntzen, a plant biotechnology expert at Arizona State University, said in an Aug. 4 [2014] telephone interview.

The tobacco plants are then infected with this new artificial virus, and antibodies are grown inside the plant. Eventually, the tobacco is ground up and the antibody is extracted, Arntzen said.

The process of growing antibodies in mammals risks transferring viruses that could infect humans, whereas “plants are so far removed, so if they had some sort of plant virus we wouldn’t get sick because viruses are host-specific,” said Qiang Chen, a plant biologist at Arizona State University in Tempe, Arizona, in a telephone interview.

There is a Canadian (?) company working on a tobacco-based vaccines including one for EVD but as the Bloomberg writers note the project is highly secret,

Another tobacco giant-backed company working on biotech drugs grown in tobacco plants is Medicago Inc. in Quebec City, which is owned by Mitsubishi Tanabe Pharma Corp. and Philip Morris. [emphasis mine]

Medicago is working on testing a vaccine for pandemic influenza and has a production greenhouse facility in North Carolina, said Jean-Luc Martre, senior director for government affairs at Medicago. Medicago is planning a final stage trial of the pandemic flu vaccine for next year, he said in a telephone interview.

The plant method is flexible and capable of making antibodies and vaccines for numerous types of viruses, said Martre. In addition to influenza, the company’s website says it is in early stages of testing products for rabies and rotavirus.

Medicago ‘‘is currently closely working with partners for the production of an Ebola antibody as well as other antibodies that are of interest for bio-defense,” he said in an e-mail. He would not disclose who the partners were. [emphasis mine]

I have checked both the English and French language versions of Medicago’s website and cannot find any information about their work on ebola. (The Bloomberg article provides a good overview of the ebola situation and more. I recommend reading it and/or the Aug. 15, 2014 posting on CTV [Canadian Television Network] which originated from an Associated Press article by Malcolm Ritter).

Moving on to more research and ebola, Dexter Johnson in an Aug. 14, 2014 posting (on his Nanoclast blog on the IEEE [Institute of Electrical and Electronics Engineers] website,) describes some work from Northeastern University (US), Note: Links have been removed,

With the Ebola virus death toll now topping 1000 and even the much publicized experimental treatment ZMapp failing to save the life of a Spanish missionary priest who was treated with it, it is clear that scientists need to explore new ways of fighting the deadly disease. For researchers at Northeastern University in Boston, one possibility may be using nanotechnology.

“It has been very hard to develop a vaccine or treatment for Ebola or similar viruses because they mutate so quickly,” said Thomas Webster, the chair of Northeastern’s chemical engineering department, in a press release. “In nanotechnology we turned our attention to developing nanoparticles that could be attached chemically to the viruses and stop them from spreading.”

Webster, along with many researchers in the nanotechnology community, have been trying to use gold nanoparticles, in combination with near-infrared light, to kill cancer cells with heat. The hope is that the same approach could be used to kill the Ebola virus.

There is also an Aug. 6, 2014 Northeastern University news release by Joe O’Connell describing the technique being used by Webster’s team,

… According to Web­ster, gold nanopar­ti­cles are cur­rently being used to treat cancer. Infrared waves, he explained, heat up the gold nanopar­ti­cles, which, in turn, attack and destroy every­thing from viruses to cancer cells, but not healthy cells.

Rec­og­nizing that a larger sur­face area would lead to a quicker heat-​​up time, Webster’s team cre­ated gold nanos­tars. “The star has a lot more sur­face area, so it can heat up much faster than a sphere can,” Web­ster said. “And that greater sur­face area allows it to attack more viruses once they absorb to the par­ti­cles.” The problem the researchers face, how­ever, is making sure the hot gold nanopar­ti­cles attack the virus or cancer cells rather than the healthy cells.

At this point, there don’t seem to be any curative measures generally available although some are available experimentally in very small quantities.

Astonishing observation about gold nanoparticles and self-assembly

An Aug. 4, 2014 news item on ScienceDaily features research on self-assembling gold nanoparticles from Helmholtz-Zentrum Berlin für Materialien und Energie (HZB) and Humboldt-Universität zu Berlin (HU, Berlin),

Researchers at HZB in co-operation with Humboldt-Universität zu Berlin (HU, Berlin) have made an astonishing observation: they were investigating the formation of gold nanoparticles in a solvent and observed that the nanoparticles had not distributed themselves uniformly, but instead were self-assembled into small clusters.

An Aug. 4, 2014 HZB press release (also on EurekAlert), which originated the news item, provides additional technical information about the equipment used to make the observations,

This was determined using Small-Angle X-ray Scattering (SAXS) at BESSY II. A thorough examination with an [a transmission] electron microscope (TEM) confirmed their result. “The research on this phenomenon is now proceeding because we are convinced that such nanoclusters lend themselves as catalysts, whether in fuel cells, in photocatalytic water splitting, or for other important reactions in chemical engineering”, explains Dr. Armin Hoell of HZB. The results have just appeared in two peer reviewed international academic journals.

“What is special about the new process is that it is extremely simple and works with an environmentally friendly and inexpensive solvent”, explains Professor Klaus Rademann from HU Berlin. The solvent actually consists of two powders that one would sooner expect to find in agriculture that in a research laboratory: a supplement in chicken feed (choline chloride, aka vitamin B), and urea. British colleagues discovered a few years ago that mixing the two powders forms a transparent liquid able to dissolve metal oxides and heavy metals, called deep eutectic solvent (DES). The researchers in Berlin then positioned above the solvent gold foil that they could bombard with ions of noble gas in order to detach individual atoms of gold. This is how nanoparticles initially formed that distributed themselves in the solvent.

The researchers did not expect what happened next (from the press release),

The longer the bombardment (sputtering) of the gold foil lasted, the larger the nanoparticles could become, the scientists reasoned. However, this was not the case: the particles ceased growing at five nanometres. Instead, an increasing number of nanoparticles formed over longer sputtering times. The second surprise: these nanoparticles did not distribute themselves uniformly in the liquid, but instead self-assembled into small groups or clusters that could consist of up to twelve nanoparticles.

These kinds of observations cannot be easily made under a microscope, of course, but require instead an indirect, statistical approach: “Using small-angle X-ray scattering at BESSY II, we were not only able to ascertain that the nanoparticles are all around five nanometres in diameter, but also measure what the separations between them are. From these measurements, we found the nanoparticles arrange themselves into clusters”, explains Hoell.

“We ran computer models in advance of how the nanoparticles could distribute themselves in the solution to better understand the measurement results, and then compared the results of the simulation with the results of the small-angle X-ray scattering”, explains Dr. Vikram Singh Raghuwanshi, who works as a postdoc at HU Berlin as well as HZB. An image from the cryogenic transmission electron microscope that colleagues at HU prepared confirmed their findings. “But we could not have achieved this result using only electron microscopy, since it can only display details and sections of the specimen”, Hoell emphasised. “Small-angle X-ray scattering is indispensable for measuring general trends and averages!”

The press release concludes thusly,

It is obvious to the researchers that the special DES-solvent plays an important role in this self-organising process: various interactions between the ions of the solvent and the particles of gold result firstly in the nanoparticles reaching only a few thousand atoms in size, and secondly that they mutually attract somewhat – but only weakly – so that the small clusters arise. “We know, however, that these kinds of small clusters of nanoparticles are especially effective as catalysts for chemical reactions we want: a many-fold increase in the reaction speed due only to particle arrangement has already been demonstrated”, says Rademann.

Here are links to and citations for the two papers the team has published on their latest work,

Deep Eutectic Solvents for the Self-Assembly of Gold Nanoparticles: A SAXS, UV–Vis, and TEM Investigation by Vikram Singh Raghuwanshi, Miguel Ochmann, Armin Hoell, Frank Polzer, and Klaus Rademann. Langmuir, 2014, 30 (21), pp 6038–6046 DOI: 10.1021/la500979p Publication Date (Web): May 11, 2014

Copyright © 2014 American Chemical Society

Self-assembly of gold nanoparticles on deep eutectic solvent (DES) surfaces by V. S. Raghuwanshi, M. Ochmann, F. Polzer, A. Hoell and K. Rademann.  Chem. Commun., 2014,50, 8693-8696 DOI: 10.1039/C4CC02588A
First published online 10 Jun 2014

Both papers are behind a paywall.

This research is being presented at two conferences, one of which is taking place now (Aug.5, 2014; from the press release),

Dr. Raghuwanshi will give a talk on these results, as well as providing a preview of the catalysis research approaches now planned, at the International conference, IUCr2014, taking place from 5-12 August 2014 in Montreal, Canada.

In the coming year, HZB will incidentally be one of the hosts of the 16th International Small-Angle Scattering Conference, SAS2015.

There you have all the news.

Gold on the brain, a possible nanoparticle delivery system for drugs

A July 21, 2014 news item on Nanowerk describes special gold nanoparticles that could make drug delivery to cells easier,

A special class of tiny gold particles can easily slip through cell membranes, making them good candidates to deliver drugs directly to target cells.

A new study from MIT materials scientists reveals that these nanoparticles enter cells by taking advantage of a route normally used in vesicle-vesicle fusion, a crucial process that allows signal transmission between neurons.

A July 21, 2014 MIT (Massachusetts Institute of Technology) news release (also on EurekAlert), which originated the news item, provides more details,

The findings suggest possible strategies for designing nanoparticles — made from gold or other materials — that could get into cells even more easily.

“We’ve identified a type of mechanism that might be more prevalent than is currently known,” says Reid Van Lehn, an MIT graduate student in materials science and engineering and one of the paper’s lead authors. “By identifying this pathway for the first time it also suggests not only how to engineer this particular class of nanoparticles, but that this pathway might be active in other systems as well.”

The paper’s other lead author is Maria Ricci of École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. The research team, led by Alfredo Alexander-Katz, an associate professor of materials science and engineering, and Francesco Stellacci from EPFL, also included scientists from the Carlos Besta Institute of Neurology in Italy and Durham University in the United Kingdom.

Most nanoparticles enter cells through endocytosis, a process that traps the particles in intracellular compartments, which can damage the cell membrane and cause cell contents to leak out. However, in 2008, Stellacci, who was then at MIT, and Darrell Irvine, a professor of materials science and engineering and of biological engineering, found that a special class of gold nanoparticles coated with a mix of molecules could enter cells without any disruption.

“Why this was happening, or how this was happening, was a complete mystery,” Van Lehn says.

Last year, Alexander-Katz, Van Lehn, Stellacci, and others discovered that the particles were somehow fusing with cell membranes and being absorbed into the cells. In their new study, they created detailed atomistic simulations to model how this happens, and performed experiments that confirmed the model’s predictions.

Gold nanoparticles used for drug delivery are usually coated with a thin layer of molecules that help tune their chemical properties. Some of these molecules, or ligands, are negatively charged and hydrophilic, while the rest are hydrophobic. The researchers found that the particles’ ability to enter cells depends on interactions between hydrophobic ligands and lipids found in the cell membrane.

Cell membranes consist of a double layer of phospholipid molecules, which have hydrophobic lipid tails and hydrophilic heads. The lipid tails face in toward each other, while the hydrophilic heads face out.

In their computer simulations, the researchers first created what they call a “perfect bilayer,” in which all of the lipid tails stay in place within the membrane. Under these conditions, the researchers found that the gold nanoparticles could not fuse with the cell membrane.

However, if the model membrane includes a “defect” — an opening through which lipid tails can slip out — nanoparticles begin to enter the membrane. When these lipid protrusions occur, the lipids and particles cling to each other because they are both hydrophobic, and the particles are engulfed by the membrane without damaging it.

In real cell membranes, these protrusions occur randomly, especially near sites where proteins are embedded in the membrane. They also occur more often in curved sections of membrane, because it’s harder for the hydrophilic heads to fully cover a curved area than a flat one, leaving gaps for the lipid tails to protrude.

“It’s a packing problem,” Alexander-Katz says. “There’s open space where tails can come out, and there will be water contact. It just makes it 100 times more probable to have one of these protrusions come out in highly curved regions of the membrane.”

This phenomenon appears to mimic a process that occurs naturally in cells — the fusion of vesicles with the cell membrane. Vesicles are small spheres of membrane-like material that carry cargo such as neurotransmitters or hormones.

The similarity between absorption of vesicles and nanoparticle entry suggests that cells where a lot of vesicle fusion naturally occurs could be good targets for drug delivery by gold nanoparticles. The researchers plan to further analyze how the composition of the membranes and the proteins embedded in them influence the absorption process in different cell types. “We want to really understand all the constraints and determine how we can best design nanoparticles to target particular cell types, or regions of a cell,” Van Lehn says.

Here’s a link to and a citation for the paper,

Lipid tail protrusions mediate the insertion of nanoparticles into model cell membranes by Reid C. Van Lehn, Maria Ricci, Paulo H.J. Silva, Patrizia Andreozzi, Javier Reguera, Kislon Voïtchovsky, Francesco Stellacci, & Alfredo Alexander-Katz. Nature Communications 5, Article number: 4482 doi:10.1038/ncomms5482 Published 21 July 2014

This article is behind a paywall but there is a free preview available via ReadCube Access.

I last featured this multi-country team’s work on gold nanoparticles in an Aug. 23, 2013 posting.

Canadian researchers develop test for exposure to nanoparticles*

The Canadian Broadcasting Corporation’s online news features a May 21, 2014 article by Emily Chung regarding research from the University of Toronto that may enable a simple skin test for determining nanoparticle exposure,

Canadian researchers have developed the first test for exposure to nanoparticles — new chemical technology found in a huge range of consumer products — that could potentially be used on humans.

Warren Chan, a University of Toronto [U of T] chemistry professor, and his team developed the skin test after noticing that some mice changed colour and others became fluorescent (that is, they glowed when light of certain colours were shone on them) after being exposed to increasing levels of different kinds of nanoparticles. The mice were being used in research to develop cancer treatments involving nanoparticles.

There is some evidence that certain types and levels of exposure may be harmful to human health. But until now, it has been hard to link exposure to health effects, partly due to the challenge of measuring exposure.

“There’s no way to determine how much [sic] nanoparticles you’ve been exposed to,” said Chan in an interview with CBCNews.ca.

There was one way to measure nanoparticle exposure in mice —  but it required the animals to be dead. At that point, they would be cut open and tests could be run on organs such as the liver and spleen where nanoparticles accumulate.

A May 14, 2014 article by Nancy Owano on phys.org provides more details (Note: Links have been removed),

They [researchers] found that different nanoparticles are visible through the skin under ambient or UV light. They found that after intravenous injection of fluorescent nanoparticles, they accumulate and can be observed through the skin. They also found that the concentration of these nanoparticles can be directly correlated to the injected dose and their accumulations in other organs.

In their discussion over selecting nanoparticles used in mouse skin, they said, “Gold nanoparticles are commonly used in molecular diagnostics and drug delivery applications. These nanomaterials were selected for our initial studies as they are easily synthesized, have a distinct ruby color and can be quantified by inductively coupled plasma atomic emission spectroscopy (ICP-AES).”

Work involved in the study included designing and performing experiments, pathological analysis, and data analysis. Their discovery could be used to better predict how nanoparticles behave in the body.

Here’s a link to and a citation for the paper,

Nanoparticle exposure in animals can be visualized in the skin and analysed via skin biopsy by Edward A. Sykes, Qin Dai, Kim M. Tsoi, David M. Hwang & Warren C. W. Chan. Nature Communications 5, Article number: 3796 doi:10.1038/ncomms4796 Published 13 May 2014

This paper is behind a paywall.

* Posting’s head changed from ‘Canadians and exposure to nanoparticles; to the more descriptive ‘Canadian researchers develop test for exposure to nanoparticles’., May 27, 2014.

Nickel-eating plant in the Philippines

For anyone interested in phytoremediation and/or phytomining, this news from the Philippines is quite exciting (from a May 9, 2014 news release on EurekAlert, Note: A link has been removed, (also on ScienceDaily),

Scientists from the University of the Philippines, Los Baños (UPLB) have discovered a new plant species with an unusual lifestyle — it eats nickel for a living — accumulating up to 18,000 ppm of the metal in its leaves without itself being poisoned, says Professor Edwino Fernando, lead author of the report. Such an amount is a hundred to a thousand times higher than in most other plants. The study was published in the open access journal PhytoKeys.

The new species is called Rinorea niccolifera, reflecting its ability to absorb nickel in very high amounts. Nickel hyperaccumulation is such a rare phenomenon with only about 0.5–1% of plant species native to nickel-rich soils having been recorded to exhibit the ability. Throughout the world, only about 450 species are known with this unusual trait, which is still a small proportion of the estimated 300,000 species of vascular plants.

A May 9, 2014 Penfold Publishers news release, which originated the items elsewhere, provides more details and an image of the nickel-eating plant,

The new species, according to Dr Marilyn Quimado, one of the lead scientists of the research team, was discovered on the western part of Luzon Island in the Philippines, an area known for soils rich in heavy metals.

“Hyperacccumulator plants have great potentials for the development of green technologies, for example, ‘phytoremediation’ and ‘phytomining’”, explains Dr Augustine Doronila of the School of Chemistry, University of Melbourne, who is also co-author of the report.

Phytoremediation refers to the use of hyperacccumulator plants to remove heavy metals in contaminated soils. Phytomining, on the other hand, is the use of hyperacccumulator plants to grow and harvest in order to recover commercially valuable metals in plant shoots from metal-rich sites. [emphasis mine]

In a previous piece about phytomining and in contrast to this news release, I suggested that phytoremediation could also function as phytomining (an idea I found elsewhere), my March 5, 2013 posting. There are also a November 22, 2012 posting and a Sept. 26, 2012 posting on the topic of phyto-mining (anyone keen to read everything here on this topic, may want to search the term both with and without hyphens).

Here is the nickel-eating plant,

Caption: This photo shows the newly described metal-eating plant, Rinorea niccolifera. Credit: Dr. Edwino S. Fernando Usage Restrictions: CC-BY 4.0

Caption: This photo shows the newly described metal-eating plant, Rinorea niccolifera.
Credit: Dr. Edwino S. Fernando
Usage Restrictions: CC-BY 4.0

Here’s a link to and a citation for the paper,

Rinorea niccolifera (Violaceae), a new, nickel-hyperaccumulating species from Luzon Island, Philippines by Edwino Fernando, Marilyn Quimado, and Augustine Doronila. PhytoKeys 37: 1–13. doi: 10.3897/phytokeys.37.7136

This paper is open access.

In a burst of curiosity I checked out the University of Philippines website and found some research bearing similarity to today’s (May 9, 2014) piece although in this case the metal being discussed is gold and the researchers are investigating the possibility of using bacteria to produce gold nanoparticles. From an April 16, 2014 article written by Miguel Victor T. Durian for the university’s Horizon magazine,

A pioneering nanotechnology study conducted by scientists at the UPLB National Institute of Molecular Biology and Biotechnology (BIOTECH) is exploring the potentials of plantgrowth- promoting bacteria (PGPB) in the biosynthesis of nanogold.

Dr. Lilia M. Fernando, Dr. Florinia E. Merca, and Dr. Erlinda S. Paterno are looking at how nanogold could be produced in large quantities using PGPB as this could bring down medical diagnostic and treatment costs especially against a dreaded disease – cancer.

“Our study primarily aimed to find a less expensive source of gold through the biosynthesis of the element by microorganisms.” Dr. Fernando explained. “Gold costs around 200 to 300 US dollars (or about Php9,000 to Php14,000), …,” Ms. Fernando added.

Furthermore, PGPB is abundantly available in the soils of the Philippines. In fact, the researchers carried out their collection of PGPB in Tarlac and Bohol. Moreover, cultivation of PGPB does not require any special incubation procedures in order to maintain its nano-size because it can survive at room temperature. This makes the cultivation of PGPB easier and less expensive compared to other microorganisms.

I look forward to hearing more about these projects as they develop.

Pretty in violet, a new antimicrobial surface that works in the dark

 Samples of silicone with the various dyes infused. Courtesy: University College of London

Samples of silicone with the various dyes infused. Courtesy: University College of London

A March 25, 2014 news item on Azonano profiles a new antimicrobial surface which works in the dark, as well as, in the light,

Researchers at UCL [University College of London] have developed a new antibacterial material which has potential for cutting hospital acquired infections. The combination of two simple dyes with nanoscopic particles of gold is deadly to bacteria when activated by light – even under modest indoor lighting. And in a first for this type of substance, it also shows impressive antibacterial properties in total darkness.

The UCL March 24, 2014 news release, which originated the news item, describes the current situation with infections in hospitals and the team’s approach to mitigating the problem,

Hospital-acquired infections are a major issue for modern medicine, with pathogens like methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile (C. diff) getting extensive publicity. Although medical establishments have stringent cleaning policies, insist on frequent hand-washing by staff, and have powerful drugs at their disposal, it is difficult to eliminate these infections unless you can make the hospital environment more hostile to microbes. Surfaces, such as door handles, medical equipment, keyboards, pens and so on are an easy route for germs to spread, even onto freshly-cleaned hands.

One possible solution to this is to develop alternative strategies such as antibacterial coatings that make surfaces less accommodating to germs. These surfaces are not like antibacterial fluids that just wash away – the goal is to make a surface which is intrinsically deadly to harmful bacteria.

“There are certain dyes that are known to be harmful to bacteria when subjected to bright light,” explains the study’s corresponding author Ivan Parkin (Head of UCL Chemistry). “The light excites electrons in them, promoting the dye molecules to an excited triplet state and ultimately produces highly reactive oxygen radicals that damage bacteria cell walls. Our project tested new combinations of these dyes along with gold nanoparticles, and simplified ways of treating surfaces which could make the technology easier and cheaper to roll out.”

The UCL news release then goes on to describe the research in some detail,

The team, tested several different combinations of the dyes crystal violet (already used to treat staph infections), methylene blue and nanogold, deposited on the surface of silicone. This flexible rubbery substance is widely used as a sealant, a coating and to build medical apparatus such as tubes, catheters and gaskets, and can also be used as protective casings for things like keyboards and telephones.

While work to create antimicrobial surfaces in the past has often concentrated on complex ways of bonding dyes to the surface, this study took a simpler approach. The researchers used an organic solvent to swell the silicone, allowing the methylene blue and gold nanoparticles to diffuse through the polymer. They then dipped the silicone into a crystal violet solution to form a thin dye layer at the polymer surface.

In their tests, in which infected surfaces were subjected to light levels similar to those measured in hospital buildings, surfaces treated with a combination of crystal violet, methylene blue and nanogold showed the most potent bactericidal effect ever observed in such a surface. Moreover, the treatment did not significantly change the properties of the silicone (for instance, how water repellent it is), and the coating was not affected by rubbing with alcohol wipes, meaning it can stand up to the repeated cleaning that goes on in hospitals, without being worn off.

“Despite contaminating the surface with far more bacteria than you would ever see in a hospital setting, placed under a normal fluorescent light bulb, the entire sample was dead in three to six hours, depending on the type of bacteria,” says the paper’s lead author, Sacha Noimark. “That was an excellent result, but the bigger surprise was the sample which we left in the dark. That sample too showed significant reductions in bacterial load, albeit over longer timescales of about three to eighteen hours. The precise mechanism by which this dark-kill works is not yet clear, though.”

This is the first time a light-activated antimicrobial surface has had any kind of effect in the dark. This, along with its unprecedented performance under hospital lighting conditions, and relatively simple and cost-effective manufacture, means that the technology is extremely promising for future applications.

The team have been granted a patent on the formulation. The work was sponsored through the UCL M3S engineering doctorate centre and co-funded by Ondine Biopharma.

Here’s a link to and a citation for the paper,

Light-activated antimicrobial surfaces with enhanced efficacy induced by a dark-activated mechanism by Sacha Noimark, Elaine Allan, and Ivan P. Parkin. Chem. Sci., 2014, Advance Article DOI: 10.1039/C3SC53186D First published online 05 Mar 2014

This article is behind a paywall. One final note, I believe the difference in publication dates, March 24, 2014 in the news release as opposed to March 5, 2014 as listed on the publication’s website, is due to the probability that the print version was published later.

Getting new information on trafficking viruses with gold nanoparticles

Finnish researchers have developed a new technique for studying viruses according to a Jan. 15, 2014 news release on EurekAlert,

Researchers at the Nanoscience Center (NSC) of University of Jyväskylä in Finland have developed a novel method to study enterovirus structures and their functions. The method will help to obtain new information on trafficking of viruses in cells and tissues as well as on the mechanisms of virus opening inside cells.

The news release explains enteroviruses and describes the technique in more detail,

Enteroviruses are pathogenic viruses infecting humans. This group consists of polioviruses, coxsackieviruses, echoviruses and rhinoviruses. Enteroviruses are the most common causes of flu, but they also cause serious symptoms such as heart muscle infections and paralysis. Recently, enteroviruses have been linked with chronic diseases such as diabetes (2).

The infection mechanisms and infectious pathways of enteroviruses are still rather poorly known. Previous studies in the group of Dr. Varpu Marjomäki at the NSC have focused on the cellular factors that are important for the infection caused by selected enteroviruses (3). The mechanistic understanding of virus opening and the release of the viral genome in cellular structures for starting new virus production is still largely lacking. Furthermore, the knowledge of infectious processes in tissues is hampered by the lack of reliable tools for detecting virus infection.

The newly developed method involves a chemical modification of a known thiol-stabilized gold nanoparticle, the so-called Au102 cluster that was first synthesized and structurally solved by the group of Roger D Kornberg in 2007 (4) and later characterized at NSC by the groups of prof. Hannu Häkkinen and prof. Mika Pettersson in collaboration with Kornberg. (5) The organic thiol surface of the Au102 particles is modified by attaching linker molecules that make a chemical bond to sulfur-containing cysteine residues that are part of the surface structure of the virus. Several tens of gold particles can bind to a single virus, and the binding pattern shows up as dark tags reflecting the overall shape and structure of the virus (see the figure). The gold particles allow for studies on the structural changes of the viruses during their lifespan.

The study showed also that the infectivity of the viruses is not compromised by the attached gold particles which indicates that the labeling method does not interfere with the normal biological functions of viruses inside cells. This facilitates new investigations on the virus structures from samples taken from inside cells during the various phases of the virus infection, and gives possibilities to obtain new information on the mechanisms of virus uncoating (opening and release of the genome). The new method allows also for tracking studies of virus pathways in tissues. This is important for further understanding of acute and chronic symptoms caused by viruses. Finally, the method is expected to be useful for developing of new antiviral vaccines that are based on virus-like particles.

The method was developed at the NSC as a wide cross-disciplinary collaboration between chemists, physicists and biologists.

Here’s an image provided by the researchers, which illustrates their work,

Left: transmission electron microscopy (TEM) image of a single CVB3 virus showing tens of gold nanoparticles attached to its surface. The particles form a distinct "tagging pattern" that reflects the shape and the structure of the virus. The TEM image can be correlated to the model of the virus (right), where the yellow spheres mark the possible binding sites of the gold particles. The diameter of the virus is about 35 nanometers (nanometer = one billionth of a millimeter). The figure is taken from the publication. Courtesy: University of Jyväskylä

Left: transmission electron microscopy (TEM) image of a single CVB3 virus showing tens of gold nanoparticles attached to its surface. The particles form a distinct “tagging pattern” that reflects the shape and the structure of the virus. The TEM image can be correlated to the model of the virus (right), where the yellow spheres mark the possible binding sites of the gold particles. The diameter of the virus is about 35 nanometers (nanometer = one billionth of a millimeter). The figure is taken from the publication. Courtesy: University of Jyväskylä

Unfortunately, the researchers have published in the Proceedings f the National Academy of Sciences (PNAS). I noted in a previous posting that this publisher has developed a time-consuming process for getting access to a paper and payment options for reading it. I can provide a link to and a citation to the abstract for this paper but I’m not willing to spend several minutes trying to bypass the block they’ve placed on accessing papers and their payment options,

Site-specific targeting of enterovirus capsid by functionalized monodisperse gold nanoclusters by Varpu Marjomäki, Tanja Lahtinen, Mari Martikainen, Jaakko Koivisto, Sami Malola, Kirsi Salorinne, Mika Pettersson, and Hannu Häkkinenb. Proc. Natl. Acad. Sci. USA (2014), www.pnas.org/cgi/doi/10.1073/pnas.1310973111.

The University of Jyväskylä Jan. ??, 2014 news release about this work provides references (scroll down) to previous papers published on this work.

A planet-satellite model for nanoparticles

For anyone who visualizes atoms as planets (many of us were taught to think of atoms and their electrons in that way) then, the planet-satellite model for nanoparticles proposed by scientists at the Nanosystems Initiative Munich (NIM) will have a comforting familiarity, Here’s the model as per a Dec. 13, 2013 news item from Nanowerk,

Nanosystems Initiative Munich (NIM) physicists have developed a “planet-satellite model” to precisely connect and arrange nanoparticles in three-dimensional structures. Like photosystems of plants and algae, the model might in future serve to collect and convert energy.

If the scientists‘ nanoparticles were one million times larger, the laboratory would look like an arts and crafts room at Christmas time: gold, silver and colorful shiny spheres in different sizes and filaments in various lengths. For at the center of the nanoscale “planet-satellite model” there is a gold particle which is orbited by other nanoparticles made of silver, cadmium selenide or organic dyes.

A Dec. 2, 2013 NIM press release, which originated the news item, describes the proposed model in detail,

As if by magic, cleverly designed DNA strands connect the satellites with the central planet in a very precise manner. The technique behind this, called “DNA origami”, is a specialty of physics professor Tim Liedl (LMU Munich) and his team. The expertise on the optical characterization of the individual nanosystems is contributed by Professor Jochen Feldmann, Chair of Photonics and Optoelectronics at LMU and Coordinator of the Nanosystems Initiative Munich (NIM).

Large or small, near or far

A distinctive feature of the new model is the modular assembly system which allows the scientists to modify all aspects of the structure very easily and in a controlled manner: the size of the central nanoparticle, the types and sizes of the “satellites” and the distance between planet and satellite particle. It also enables the physicists to adapt and optimize their system for other purposes.

Artificial photosystem

Metals, semiconductors or fluorescent organic molecules serve as satellites. Thus, like the antenna molecules in natural photosystems, such satellite elements might in future be organized to collect light energy and transfer it to a catalytic reaction center where it is converted into another form of energy. For the time being, however, the model allows the scientists to investigate basic physical effects such as the so-called quenching process, which refers to the changing fluorescence intensity of a dye molecule as a function of the distance to the central gold nanoparticle.

“The modular assembly principle and the high yield we obtained in the production of the planet-satellite systems were the crucial factors for reliably investigating this well-known effect with the new methods,” explains Robert Schreiber, lead author of the study.

A whole new cosmos

In addition, the scientists succeeded in joining individual planet-satellite units together into larger structures, combining them as desired. This way, it might be possible to develop complex and functional three-dimensional nanosystems in future, which could be used as directed energy funnels, in Raman spectroscopy or as nanoporous materials for catalytic applications.

The physicists have supplied an image illustrating their model,

 

[downloaded from http://www.nano-initiative-munich.de/index.php?eID=tx_cms_showpic&file=uploads%2Fpics%2FBasiccover_6_Zeilen_02.jpg&md5=aec790fc11262dc94b41a440fa6788baeacfac97&parameters[0]=YTo0OntzOjU6IndpZHRoIjtzOjQ6IjUwMG0iO3M6NjoiaGVpZ2h0IjtzOjM6IjUw&parameters[1]=MCI7czo3OiJib2R5VGFnIjtzOjI0OiI8Ym9keSBiZ0NvbG9yPSIjZmZmZmZmIj4i&parameters[2]=O3M6NDoid3JhcCI7czozNzoiPGEgaHJlZj0iamF2YXNjcmlwdDpjbG9zZSgpOyI%2B&parameters[3]=IHwgPC9hPiI7fQ%3D%3D] Courtesy NIM

[downloaded from http://www.nano-initiative-munich.de/index.php?eID=tx_cms_showpic&file=uploads%2Fpics%2FBasiccover_6_Zeilen_02.jpg&md5=aec790fc11262dc94b41a440fa6788baeacfac97&parameters[0]=YTo0OntzOjU6IndpZHRoIjtzOjQ6IjUwMG0iO3M6NjoiaGVpZ2h0IjtzOjM6IjUw&parameters[1]=MCI7czo3OiJib2R5VGFnIjtzOjI0OiI8Ym9keSBiZ0NvbG9yPSIjZmZmZmZmIj4i&parameters[2]=O3M6NDoid3JhcCI7czozNzoiPGEgaHJlZj0iamF2YXNjcmlwdDpjbG9zZSgpOyI%2B&parameters[3]=IHwgPC9hPiI7fQ%3D%3D] Courtesy NIM

 

Here’s a link to and a citation for the researchers’ paper,

Hierarchical assembly of metal nanoparticles, quantum dots and organic dyes using DNA origami scaffolds by Robert Schreiber, Jaekwon Do, Eva-Maria Roller, Tao Zhang, Verena J. Schüller, Philipp C. Nickels, Jochen Feldmann, & Tim Liedl. Nature Nanotechnology (2013) doi:10.1038/nnano.2013.253 Published online 01 December 2013

It is behind a paywall but you can preview it for free via ReadCube Access.

Stabilizing or destabilitizing gold nanoparticles

Every once in a while I stumble across a ‘nanotechnology’ news release from Oregon (either Oregon State University or the University of Oregon) and as I recall it’s always environment-focused. The latest in an almost complete change-of-pace is, a Dec. 9, 2013 University of Oregon news release (also on EurekAlert) profiling some work on gold nanoparticles and nanoelectronics,

University of Oregon chemists studying the structure of ligand-stabilized gold nanoparticles have captured fundamental new insights about their stability. The information, they say, could help to maintain a desired, integral property in nanoparticles used in electronic devices, where stability is important, or to design them so they readily condense into thin films for such things as inks or catalysts in electronic or solar devices.

The news release goes on to detail the work,

They focused on nanoparticles less than two nanometers in diameter — the smallest studied to date — to better understand structural stability of these tiny particles being engineered for use in electronics, medicine and other materials. Whether a nanoparticle needs to remain stable or condense depends on how they are being used. Those used as catalysts in industrial chemical processing or quantum dots for lighting need to remain intact; if they are precursors for coatings in solar devices or for printing ink, nanoparticles need to be unstable so they sinter and condense into a thin mass.

For their experiments, Smith and Hutchison produced gold nanoparticles in four well-controlled sizes, ranging from 0.9 nanometers to 1.5 nanometers, and analyzed ligand loss and sintering with thermogravimetric analysis and differential scanning calorimetry, and examined the resulting films by scanning electron microscopy and X-ray photoelectron spectroscopy. As the nanoparticles were heated at 5 degrees Celsius per minute, from room temperature to 600 degrees Celsius, the nanoparticles began to transform near 150 degrees Celsius.

The researchers found that smaller nanoparticles have better structural integrity than larger-sized particles that have been tested. In other words, Hutchison said, they are less likely to lose their ligands and bind together. “If you have unstable particles, then the property you want is fleeting,” he said. “Either the light emission degrades over time and you’re done, or the metal becomes inactive and you’re done. In that case, you want to preserve the function and keep the particles from aggregating.”The opposite is desired for Hutchison and others working in the National Science Foundation-funded Center for Sustainable Materials Chemistry, a multi-universities collaboration led by the UO and Oregon State University. Researchers there are synthesizing nanoparticles as precursors for thin films.

“We want solution precursors that can lead to inorganic thin films for use in electronics and solar industries,” said Hutchison, who also is a member of the UO Materials Science Institute.

“In this case, we want to know how to keep our nanoparticles or other precursors stable enough in solution so that we can work with them, using just a tiny amount of additional energy to make them unstable so that they condense into a film — where the property that you want comes from the extended solid that is generated, not from the nanoparticles themselves.”

The research, Hutchison said, identified weak sites on nanoparticles where ligands might pop off. If only a small amount do so, he said, separate nanoparticles are more likely to come together and begin the sintering process to create thin films.

“That’s a really stabilizing effect that, in turn, kicks out all these ligands on the outside,” he said. “The surface area decreases quickly and the particles get bigger, but now all the extra ligands gets excluded into the film and then, over time, the ligands vaporize and go away.”

The coming apart, however, is a “catastrophic failure” if protecting against sintering is the goal. It may be possible to use the findings, he said, to explore ways to strengthen nanoparticles, such as developing ligands that bind in at least two sites or avoiding volatile ligands.

The process, as studied, produced porous gold films. “A next step might be to study how to manipulate the process to get a more dense film if that is desired,” Hutchison said. Understanding how nanoparticles respond to certain conditions, such as changing temperatures, he added, may help researchers reduce waste in the manufacturing process.

As I hinted earlier, this work retains an ‘environment focus’,

“Researchers at the University of Oregon are re-engineering the science, manufacturing and business processes behind critical products,” said Kimberly Andrews Espy, vice president for research and innovation and dean of the UO Graduate School. “This research analyzing the structural stability of nanoparticles by Dr. Hutchison and his team has the potential to improve the engineering of electronics, medicine and other materials, helping to foster a sustainable future for our planet and its people.” [emphasis mine]

Here’s a link to and a citation for the paper,

Transformations during Sintering of Small (Dcore < 2 nm) Ligand-Stabilized Gold Nanoparticles: Influence of Ligand Functionality and Core Size by Beverly L. Smith and James E. Hutchison. J. Phys. Chem. C, 2013, 117 (47), pp 25127–25137 DOI: 10.1021/jp408111v Publication Date (Web): October 24, 2013
Copyright © 2013 American Chemical Society

This paper is behind a paywall.

Bejweled and bedazzled but not bewitched, bothered, or bewildered at Northwestern University

When discussing DNA (deoxyribonucleic acid) one doesn’t usually expect to encounter gems as one does in a Nov. 28, 2013 news item on Azonano,

Nature builds flawless diamonds, sapphires and other gems. Now a Northwestern University [located in Chicago, Illinois, US] research team is the first to build near-perfect single crystals out of nanoparticles and DNA, using the same structure favored by nature.

The Nov. 27, 2013 Northwestern University news release by Megan Fellman (also on EurekAlert), which originated the news item,, explains why single crystals are of such interest,

“Single crystals are the backbone of many things we rely on — diamonds for beauty as well as industrial applications, sapphires for lasers and silicon for electronics,” said nanoscientist Chad A. Mirkin. “The precise placement of atoms within a well-defined lattice defines these high-quality crystals.

“Now we can do the same with nanomaterials and DNA, the blueprint of life,” Mirkin said. “Our method could lead to novel technologies and even enable new industries, much as the ability to grow silicon in perfect crystalline arrangements made possible the multibillion-dollar semiconductor industry.”

His research group developed the “recipe” for using nanomaterials as atoms, DNA as bonds and a little heat to form tiny crystals. This single-crystal recipe builds on superlattice techniques Mirkin’s lab has been developing for nearly two decades.

(I wrote about Mirkin’s nanoparticle DNA work in the context of his proposed periodic table of modified nucleic acid nanoparticles in a July 5, 2013 posting.) The news release goes on to describe Mirkin’s most recent work,

In this recent work, Mirkin, an experimentalist, teamed up with Monica Olvera de la Cruz, a theoretician, to evaluate the new technique and develop an understanding of it. Given a set of nanoparticles and a specific type of DNA, Olvera de la Cruz showed they can accurately predict the 3-D structure, or crystal shape, into which the disordered components will self-assemble.

The general set of instructions gives researchers unprecedented control over the type and shape of crystals they can build. The Northwestern team worked with gold nanoparticles, but the recipe can be applied to a variety of materials, with potential applications in the fields of materials science, photonics, electronics and catalysis.

A single crystal has order: its crystal lattice is continuous and unbroken throughout. The absence of defects in the material can give these crystals unique mechanical, optical and electrical properties, making them very desirable.

In the Northwestern study, strands of complementary DNA act as bonds between disordered gold nanoparticles, transforming them into an orderly crystal. The researchers determined that the ratio of the DNA linker’s length to the size of the nanoparticle is critical.

“If you get the right ratio it makes a perfect crystal — isn’t that fun?” said Olvera de la Cruz, who also is a professor of chemistry in the Weinberg College of Arts and Sciences. “That’s the fascinating thing, that you have to have the right ratio. We are learning so many rules for calculating things that other people cannot compute in atoms, in atomic crystals.”

The ratio affects the energy of the faces of the crystals, which determines the final crystal shape. Ratios that don’t follow the recipe lead to large fluctuations in energy and result in a sphere, not a faceted crystal, she explained. With the correct ratio, the energies fluctuate less and result in a crystal every time.

“Imagine having a million balls of two colors, some red, some blue, in a container, and you try shaking them until you get alternating red and blue balls,” Mirkin explained. “It will never happen.

“But if you attach DNA that is complementary to nanoparticles — the red has one kind of DNA, say, the blue its complement — and now you shake, or in our case, just stir in water, all the particles will find one another and link together,” he said. “They beautifully assemble into a three-dimensional crystal that we predicted computationally and realized experimentally.”

To achieve a self-assembling single crystal in the lab, the research team reports taking two sets of gold nanoparticles outfitted with complementary DNA linker strands. Working with approximately 1 million nanoparticles in water, they heated the solution to a temperature just above the DNA linkers’ melting point and then slowly cooled the solution to room temperature, which took two or three days.

The very slow cooling process encouraged the single-stranded DNA to find its complement, resulting in a high-quality single crystal approximately three microns wide. “The process gives the system enough time and energy for all the particles to arrange themselves and find the spots they should be in,” Mirkin said.

The researchers determined that the length of DNA connected to each gold nanoparticle can’t be much longer than the size of the nanoparticle. In the study, the gold nanoparticles varied from five to 20 nanometers in diameter; for each, the DNA length that led to crystal formation was about 18 base pairs and six single-base “sticky ends.”

“There’s no reason we can’t grow extraordinarily large single crystals in the future using modifications of our technique,” said Mirkin, who also is a professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering and director of Northwestern’s International Institute for Nanotechnology.

Here’s a link to and a citation for the published paper,

DNA-mediated nanoparticle crystallization into Wulff polyhedra by Evelyn Auyeung, Ting I. N. G. Li, Andrew J. Senesi, Abrin L. Schmucker, Bridget C. Pals, Monica Olvera de la Cruz, & Chad A. Mirkin. Nature (2013) doi:10.1038/nature12739 Published online 27 November 2013

This article is behind a paywall.

Points to anyone who recognized the song title (Bewitched, Bothered and Bewildered) embedded in the head for this posting.