Tag Archives: gold nanoparticles

Nano and stem cell differentiation at Rutgers University (US)

A Nov. 14, 2014 news item on Azonano features a nanoparticle-based platform for differentiating stem cells,

Rutgers University Chemistry Associate Professor Ki-Bum Lee has developed patent-pending technology that may overcome one of the critical barriers to harnessing the full therapeutic potential of stem cells.

A Nov. 1, 2104 Rutgers University news release, which originated the news item, describes the challenge in more detail,

One of the major challenges facing researchers interested in regenerating cells and growing new tissue to treat debilitating injuries and diseases such as Parkinson’s disease, heart disease, and spinal cord trauma, is creating an easy, effective, and non-toxic methodology to control differentiation into specific cell lineages. Lee and colleagues at Rutgers and Kyoto University in Japan have invented a platform they call NanoScript, an important breakthrough for researchers in the area of gene expression. Gene expression is the way information encoded in a gene is used to direct the assembly of a protein molecule, which is integral to the process of tissue development through stem cell therapeutics.

Stem cells hold great promise for a wide range of medical therapeutics as they have the ability to grow tissue throughout the body. In many tissues, stem cells have an almost limitless ability to divide and replenish other cells, serving as an internal repair system.

Transcription factor (TF) proteins are master regulators of gene expression. TF proteins play a pivotal role in regulating stem cell differentiation. Although some have tried to make synthetic molecules that perform the functions of natural transcription factors, NanoScript is the first nanomaterial TF protein that can interact with endogenous DNA. …

“Our motivation was to develop a highly robust, efficient nanoparticle-based platform that can regulate gene expression and eventually stem cell differentiation,” said Lee, who leads a Rutgers research group primarily focused on developing and integrating nanotechnology with chemical biology to modulate signaling pathways in cancer and stem cells. “Because NanoScript is a functional replica of TF proteins and a tunable gene-regulating platform, it has great potential to do exactly that. The field of stem cell biology now has another platform to regulate differentiation while the field of nanotechnology has demonstrated for the first time that we can regulate gene expression at the transcriptional level.”

Here’s an image illustrating NanoScript and gold nanoparticles,

Courtesy Rutgers University

Courtesy Rutgers University

The news release goes on to describe the platform’s use of gold nanoparticles,

NanoScript was constructed by tethering functional peptides and small molecules called synthetic transcription factors, which mimic the individual TF domains, onto gold nanoparticles.

“NanoScript localizes within the nucleus and initiates transcription of a reporter plasmid by up to 30-fold,” said Sahishnu Patel, Rutgers Chemistry graduate student and co-author of the ACS Nano publication. “NanoScript can effectively transcribe targeted genes on endogenous DNA in a nonviral manner.”

Lee said the next step for his research is to study what happens to the gold nanoparticles after NanoScript is utilized, to ensure no toxic effects arise, and to ensure the effectiveness of NanoScript over long periods of time.

“Due to the unique tunable properties of NanoScript, we are highly confident this platform not only will serve as a desirable alternative to conventional gene-regulating methods,” Lee said, “but also has direct employment for applications involving gene manipulation such as stem cell differentiation, cancer therapy, and cellular reprogramming. Our research will continue to evaluate the long-term implications for the technology.”

Lee, originally from South Korea, joined the Rutgers faculty in 2008 and has earned many honors including the NIH Director’s New Innovator Award. Lee received his Ph.D. in Chemistry from Northwestern University where he studied with Professor Chad. A. Mirkin, a pioneer in the coupling of nanotechnology and biomolecules. Lee completed his postdoctoral training at The Scripps Research Institute with Professor Peter G. Schultz. Lee has served as a Visiting Scholar at both Princeton University and UCLA Medical School.

The primary interest of Lee’s group is to develop and integrate nanotechnologies and chemical functional genomics to modulate signaling pathways in mammalian cells towards specific cell lineages or behaviors. He has published more than 50 articles and filed for 17 corresponding patents.

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

NanoScript: A Nanoparticle-Based Artificial Transcription Factor for Effective Gene Regulation by Sahishnu Patel, Dongju Jung, Perry T. Yin, Peter Carlton, Makoto Yamamoto, Toshikazu Bando, Hiroshi Sugiyama, and Ki-Bum Lee. ACS Nano, 2014, 8 (9), pp 8959–8967 DOI: 10.1021/nn501589f Publication Date (Web): August 18, 2014
Copyright © 2014 American Chemical Society

This paper is behind a paywall.

Faster, cheaper, and just as good—nanoscale device for measuring cancer drug methotrexate

Lots of cancer drugs can be toxic if the dosage is too high for individual metabolisms, which can vary greatly in their ability to break drugs down. The University of Montréal (Université de Montréal) has announced a device that could help greatly in making the technology to determine toxicity in the bloodstream faster and cheaper according to an Oct. 27, 2014 news item on Nanowerk,

In less than a minute, a miniature device developed at the University of Montreal can measure a patient’s blood for methotrexate, a commonly used but potentially toxic cancer drug. Just as accurate and ten times less expensive than equipment currently used in hospitals, this nanoscale device has an optical system that can rapidly gauge the optimal dose of methotrexate a patient needs, while minimizing the drug’s adverse effects. The research was led by Jean-François Masson and Joelle Pelletier of the university’s Department of Chemistry.

An Oct. 27, 2014 University of Montréal news release, which originated the news item, provides more specifics about the cancer drug being monitored and the research that led to the new device,

Methotrexate has been used for many years to treat certain cancers, among other diseases, because of its ability to block the enzyme dihydrofolate reductase (DHFR). This enzyme is active in the synthesis of DNA precursors and thus promotes the proliferation of cancer cells. “While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,” Masson explained.

Until now, monitoring has been done in hospitals with a device using fluorescent bioassays to measure light polarization produced by a drug sample. “The operation of the current device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated,” Masson said.

Six years ago, Joelle Pelletier, a specialist of the DHFR enzyme, and Jean-François Masson, an expert in biomedical instrument design, investigated how to simplify the measurement of methotrexate concentration in patients.

Gold nanoparticles on the surface of the receptacle change the colour of the light detected by the instrument. The detected colour reflects the exact concentration of the drug in the blood sample. In the course of their research, they developed and manufactured a miniaturized device that works by surface plasmon resonance. Roughly, it measures the concentration of serum (or blood) methotrexate through gold nanoparticles on the surface of a receptacle. In “competing” with methotrexate to block the enzyme, the gold nanoparticles change the colour of the light detected by the instrument. And the colour of the light detected reflects the exact concentration of the drug in the blood sample.

The accuracy of the measurements taken by the new device were compared with those produced by equipment used at the Maisonneuve-Rosemont Hospital in Montreal. “Testing was conclusive: not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices,” Masson said. Moreover, the comparative tests were performed by laboratory technicians who were not experienced with surface plasmon resonance and did not encounter major difficulties in operating the new equipment or obtaining the same conclusive results as Masson and his research team.

In addition to producing results in real time, the device designed by Masson is small and portable and requires little manipulation of samples. “In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualized and optimal doses while minimizing the risk of complications,” Masson said. Another benefit, and a considerable one: “While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost ten times less, around $10,000.”

For those who prefer to read the material in French here’s a link to ‘le 27 Octobre 2014 communiqué de nouvelles‘.

Here’s a prototype of the device,

Les nanoparticules d’or situées à la surface de la languette réceptrice modifient la couleur de la lumière détectée par l’instrument. La couleur captée reflète la concentration exacte du médicament contenu dans l’échantillon sanguin. Courtesy  Université de Montréal

Les nanoparticules d’or situées à la surface de la languette réceptrice modifient la couleur de la lumière détectée par l’instrument. La couleur captée reflète la concentration exacte du médicament contenu dans l’échantillon sanguin. Courtesy Université de Montréal

There is no indication as to when this might come to market, in English  or in French.

Gold nanorods and mucus

Mucus can kill. Most of us are lucky enough to produce mucus appropriate for our bodies’ needs but people who have cystic fibrosis and other kinds of lung disease suffer greatly from mucus that is too thick to pass easily through the body. An Oct. 9, 2014 Optical Society of America (OSA) news release (also on EurekAlert) ‘shines’ a light on the topic of mucus and viscosity,

Some people might consider mucus an icky bodily secretion best left wrapped in a tissue, but to a group of researchers from the University of North Carolina at Chapel Hill, snot is an endlessly fascinating subject. The team has developed a way to use gold nanoparticles and light to measure the stickiness of the slimy substance that lines our airways.  The new method could help doctors better monitor and treat lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.

“People who are suffering from certain lung diseases have thickened mucus,” explained Amy Oldenburg, a physicist at the University of North Carolina at Chapel Hill whose research focuses on biomedical imaging systems. “In healthy adults, hair-like cell appendages called cilia line the airways and pull mucus out of the lungs and into the throat. But if the mucus is too viscous it can become trapped in the lungs, making breathing more difficult and also failing to remove pathogens that can cause chronic infections.”

Doctors can prescribe mucus-thinning drugs, but have no good way to monitor how the drugs affect the viscosity of mucus at various spots inside the body. This is where Oldenburg and her colleagues’ work may help.

The researchers placed coated gold nanorods on the surface of mucus samples and then tracked the rods’ diffusion into the mucus by illuminating the samples with laser light and analyzing the way the light bounced off the nanoparticles. The slower the nanorods diffused, the thicker the mucus. The team found this imaging method worked even when the mucus was sliding over a layer of cells—an important finding since mucus inside the human body is usually in motion.

“The ability to monitor how well mucus-thinning treatments are working in real-time may allow us to determine better treatments and tailor them for the individual,” said Oldenburg.

It will likely take five to 10 more years before the team’s mucus measuring method is tested on human patients, Oldenburg said. Gold is non-toxic, but for safety reasons the researchers would want to ensure that the gold nanorods would eventually be cleared from a patient’s system.

“This is a great example of interdisciplinary work in which optical scientists can meet a specific need in the clinic,” said Nozomi Nishimura, of Cornell University … . “As these types of optical technologies continue to make their way into medical practice, it will both expand the market for the technology as well as improve patient care.”

The team is also working on several lines of ongoing study that will some day help bring their monitoring device to the clinic. They are developing delivery methods for the gold nanorods, studying how their imaging system might be adapted to enter a patient’s airways, and further investigating how mucus flow properties differ throughout the body.

This work is being presented at:

The research team will present their work at The Optical Society’s (OSA) 98th Annual Meeting, Frontiers in Optics, being held Oct. 19-23 [2014] in Tucson, Arizona, USA.

Presentation FTu5F.2, “Imaging Gold Nanorod Diffusion in Mucus Using Polarization Sensitive OCT,” takes place Tuesday, Oct. 21 at 4:15 p.m. MST [Mountain Standard Time] in the Tucson Ballroom, Salon A at the JW Marriott Tucson Starr Pass Resort.

People with cystic fibrosis tend to have short lives (from the US National Library of Medicine MedLine Plus webpage on cystic fibrosis),

Most children with cystic fibrosis stay in good health until they reach adulthood. They are able to take part in most activities and attend school. Many young adults with cystic fibrosis finish college or find jobs.

Lung disease eventually worsens to the point where the person is disabled. Today, the average life span for people with CF who live to adulthood is about 37 years.

Death is most often caused by lung complications.

I hope this work proves helpful.

Fishnet of gold atoms improves solar cell performance

Apparently they’re calling the University of Western Ontario by a new name, Western University. Given the university’s location in what is generally acknowledged as central Canada or, sometimes, as eastern Canada, this seems like a geographically confusing approach not only in Canada but elsewhere too. After all, more than one country boasts a ‘west’.

A Sept. 26, 2014 news item on Nanowerk highlights new work on improving solar cell performance (Note: A link has been removed),

Scientists at Western University [Ontario, Canada] have discovered that a small molecule created with just 144 atoms of gold can increase solar cell performance by more than 10 per cent. These findings, published recently by the high-impact journal Nanoscale (“Tessellated gold nanostructures from Au144(SCH2CH2Ph)60 molecular precursors and their use in organic solar cell enhancement”), represent a game-changing innovation that holds the potential to take solar power mainstream and dramatically decrease the world’s dependence on traditional, resource-based sources of energy, says Giovanni Fanchini from Western’s Faculty of Science.

For those of us who remember ‘times tables’, the number 144 can have a special meaning as it is the last number (’12’ times ’12’ equals ‘144’) one was obliged to memorize. At least, that was true at my school in Vancouver, Canada but perhaps not elsewhere, eh?

Getting back to the ‘fishnet’, a Sept. 25, 2014 Western University news release, which originated the news item, expands the business possibilities for this work,

Fanchini, the Canada Research Chair in Carbon-based Nanomaterials and Nano-optoelectronics, says the new technology could easily be fast-tracked and integrated into prototypes of solar panels in one to two years and solar-powered phones in as little as five years.

“Every time you recharge your cell phone, you have to plug it in,” says Fanchini, an assistant professor in Western’s Department of Physics and Astronomy. “What if you could charge mobile devices like phones, tablets or laptops on the go? Not only would it be convenient, but the potential energy savings would be significant.”

The Western researchers have already started working with manufacturers of solar components to integrate their findings into existing solar cell technology and are excited about the potential.

“The Canadian business industry already has tremendous know-how in solar manufacturing,” says Fanchini. “Our invention is modular, an add-on to the existing production process, so we anticipate a working prototype very quickly.”

The news release then gives a few technical details,

Making nanoplasmonic enhancements, Fanchini and his team use “gold nanoclusters” as building blocks to create a flexible network of antennae on more traditional solar panels to attract an increase of light. While nanotechnology is the science of creating functional systems at the molecular level, nanoplasmonics investigates the interaction of light with and within these systems.

“Picture an extremely delicate fishnet of gold,” explains Fanchini explains, noting that the antennae are so miniscule they are unseen even with a conventional optical microscope. “The fishnet catches the light emitted by the sun and draws it into the active region of the solar cell.”

According to Fanchini, the spectrum of light reflected by gold is centered on the yellow colour and matches the light spectrum of the sun making it superior for such antennae as it greatly amplifies the amount of sunlight going directly into the device.

“Gold is very robust, resilient to oxidization and not easily damaged, making it the perfect material for long-term use,” says Fanchini. “And gold can also be recycled.”

It has been known for some time that larger gold nanoparticles enhance solar cell performance, but the Western team is getting results with “a ridiculously small amount” – approximately 10,000 times less than previous studies, which is 10,000 times less expensive too.

I hope to hear about a working prototype soon. Meanwhile, here’s a link to and a citation for the paper,

Tessellated gold nanostructures from Au144(SCH2CH2Ph)60 molecular precursors and their use in organic solar cell enhancement by Reg Bauld, Mahdi Hesari, Mark S. Workentin, and Giovanni Fanchini. Nanoscale, 2014,6, 7570-7575 DOI: 10.1039/C4NR01821D
First published online 06 May 2014

This paper is behind a paywall.

One final comment, it seems like a long lead time between publication of the paper and publicity. I wonder if the paper failed to get notice in May 2014, assuming there was a campaign at the time, or if this is considered a more optimal time period for getting noticed.

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.