Category Archives: medicine

Medical isotope team at TRIUMF (Canada’s national laboratory for particle and nuclear physics) wins award

I’ve written a few times about the development of a new means for producing medical isotopes that does not require nuclear materials. (my June 10, 2014 posting and my June 9, 2013 posting,) The breakthrough was made at TRIUMF, Canada’s national laboratory for particle and nuclear physics, which is located in Vancouver, and the team which made the breakthrough is being honoured. From a Feb. 17, 2015 TRIUMF news release,

For their outstanding teamwork in realizing a solution for safe and reliable isotope production for hospitals in Canada,interdisciplinary research team CycloMed99 will be receiving a prestigious national award at a ceremony in Ottawa today [Feb. 17, 2015]. The Honourable David Johnston, Governor General of Canada, will present the NSERC  [Natural Sciences and Engineering Research Council of Canada] Brockhouse Canada Prize for Interdisciplinary Research in Science and Engineering to the team in recognition of their seamless teamwork and successes.

Drawing from expertise in physics, chemistry, and nuclear medicine, the team set out five years ago to develop a reliable, alternative means of production for a key medical isotope in order to eliminate the threat of a supply shortage – a catastrophic healthcare crisis for patients around the world. Technetium-99m (Tc-99m) is the world standard for medical imaging to diagnose cancer and heart disease. Every day, 5,000 medical procedures in
Canada and 70,000 daily worldwide depend on this isotope. With funding support from NSERC, CIHR and Natural Resources Canada, the team developed technology that uses medical cyclotrons already installed and operational in major hospitals across Canada to produce enough Tc-99m on a daily basis.

This innovation is safer and more environmentally friendly than current technology because it eliminates the need for highly enriched uranium, also avoiding the generation
of highly radioactive waste. Canada’s healthcare system would save money by producing isotopes locally under a full-cost recovery model.

The project resulted in over a dozen scientific publications, several provisional patents and a training opportunity for more than 175 individuals.

Now, the research team is focused on working with the world’s major cyclotron manufacturers to add factory-supported Tc-99m production capability to their existing product lines so the technology will become standard in future machines.

CycloMed99 is also working with a Canadian start-up company to license, transfer and sell this technology around the world. This will allow hospitals and companies with cyclotrons to retrofit their existing infrastructure with a Made in Canada solution to produce this valuable material.

Congratulations to the CycloMed99 team, recipients of the Brockhouse Canada Prize:

• Dr. Paul Schaffer, a chemist by training and Division Head, Nuclear Medicine at TRIUMF; Adjunct Professor, Dept. of Chemistry at Simon Fraser University; and Professor, Dept. of Radiology at the University of British Columbia (UBC);

• Dr. François Bénard, a clinician by training and BC Leadership Chair in Functional Cancer Imaging at the BC Cancer Agency; and Professor, Dept. of Radiology at UBC;

• Dr. Anna Celler, a medical physicist by training and Professor, Dept. of Radiology at UBC;

• Dr. Michael Kovacs, a chemist by training; PET Radiochemistry Facility Imaging Scientist at Lawson Health Research Institute; Associate Professor at Western University;

• Dr. Thomas J. Ruth, a nuclear chemist by training and researcher emeritus at TRIUMF; and Professor emeritus at UBC, and;

• Dr. John Valliant, a chemist by training and Scientific Director and CEO of the Centre for Probe Development and Commercialization; and Professor at McMaster University.

There’s more information about TRIUMF and the business aspect of this breakthrough in a Jan. 16, 2015 article by Tyler Orton for Business in Vancouver.

Tackling ‘untreatable’ brain tumours

Isreal’s Tel Aviv University (TAU) has announced research that combines a nanoparticle-platform with RNA (ribonucleic acid) interference (RNAi) therapy for a difficult to treat brain cancer. From a Feb. 24, 2015 news item on Nanowerk,

There are no effective available treatments for sufferers of Glioblastoma multiforme (GBM), the most aggressive and devastating form of brain tumor. The disease, always fatal, has a survival rate of only 6-18 months.

Now a new Tel Aviv University study may offer hope to the tens of thousands diagnosed with gliomas every year. A pioneer of cancer-busting nanoscale therapeutics, Prof. Dan Peer of TAU’s Department of Department of Cell Research and Immunology and Scientific Director of TAU’s Center for NanoMedicine has adapted an earlier treatment modality — one engineered to tackle ovarian cancer tumors — to target gliomas, with promising results.

A Feb. 24, 2015 American Friends of Tel Aviv University news release (also on EurekAlert), which originated the news item, describes how the two lead researchers came to collaborate on this project,

“I was approached by a neurosurgeon insistent on finding a solution, any solution, to a desperate situation,” said Prof. Peer. “Their patients were dying on them, fast, and they had virtually no weapons in their arsenal. Prof. Zvi Cohen heard about my earlier nanoscale research and suggested using it as a basis for a novel mechanism with which to treat gliomas.”

Dr. Cohen had acted as the primary investigator in several glioma clinical trials over the last decade, in which new treatments were delivered surgically into gliomas or into the surrounding tissues following tumor removal. “Unfortunately, gene therapy, bacterial toxin therapy, and high-intensity focused ultrasound therapy had all failed as approaches to treat malignant brain tumors,” said Dr. Cohen. “I realized that we must think differently. When I heard about Dan’s work in the field of nanomedicine and cancer, I knew I found an innovative approach combining nanotechnology and molecular biology to tackle brain cancer.”

The news release then describes the research in more detail,

Dr. Peer’s new research is based on a nanoparticle platform, which transports drugs to target sites while minimizing adverse effects on the rest of the body. Prof. Peer devised a localized strategy to deliver RNA genetic interference (RNAi) directly to the tumor site using lipid-based nanoparticles coated with the polysugar hyaluronan (HA) that binds to a receptor expressed specifically on glioma cells. Prof. Peer and his team of researchers tested the therapy in mouse models affected with gliomas and control groups treated with standard forms of chemotherapy. The results were, according to the researchers, astonishing.

“We used a human glioma implanted in mice as our preclinical model,” said Prof. Peer. “Then we injected our designed particle with fluorescent dye to monitor its success entering the tumor cells. We were pleased and astonished to find that, a mere three hours later, the particles were situated within the tumor cells.”

Rather than chemotherapy, Prof. Peer’s nanoparticles contain nucleic acid with small interference RNAs, which silence the functioning of a key protein involved in cell proliferation. “Cancer cells, always dividing, are regulated by a specific protein,” said Prof. Peer. “We thought if we could silence this gene, they would die off. It is a basic, elegant mechanism and much less toxic than chemotherapy. This protein is not expressed in normal cells, so it only works where cells are highly proliferated.”

100 days following the treatment of four injections over 30 days, 60 percent of the afflicted mice were still alive. This represents a robust survival rate for mice, whose average life expectancy is only two years. The control mice died 30-34.5 days into treatment.

“This is a proof of concept study which can be translated into a novel clinical modality,” said Prof. Peer. “While it is in early stages, the data is so promising — it would be a crime not to pursue it.”

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

Localized RNAi Therapeutics of Chemoresistant Grade IV Glioma Using Hyaluronan-Grafted Lipid-Based Nanoparticles by Zvi R. Cohen, Srinivas Ramishetti, Naama Peshes-Yaloz, Meir Goldsmith, Anton Wohl, Zion Zibly, and Dan Peer. ACS Nano, 2015, 9 (2), pp 1581–1591 DOI: 10.1021/nn506248s Publication Date (Web): January 5, 2015
Copyright © 2015 American Chemical Society

This study is behind a paywall.

McGill University (Canada) researchers build DNA nanotubes block by block

McGill University (Montréal, Québec, Canada) researchers have found a new technique for creating DNA (deoxyribonucleic acid) nanotubes according to a Feb. 24, 2015 news item on Azonano,

Researchers at McGill University have developed a new, low-cost method to build DNA nanotubes block by block – a breakthrough that could help pave the way for scaffolds made from DNA strands to be used in applications such as optical and electronic devices or smart drug-delivery systems.

A Feb. 23, 2015 McGill University news release (also on EurekAlert), which originated the news item, describes current practice and the new technique,

Many researchers, including the McGill team, have previously constructed nanotubes using a method that relies on spontaneous assembly of DNA in solution. The new technique, reported today in Nature Chemistry, promises to yield fewer structural flaws than the spontaneous-assembly method. The building-block approach also makes it possible to better control the size and patterns of the DNA structures, the scientists report.

“Just like a Tetris game, where we manipulate the game pieces with the aim of creating a horizontal line of several blocks, we can now build long nanotubes block by block,” said Amani Hariri, a PhD student in McGill’s Department of Chemistry and lead author of the study. “By using a fluorescence microscope we can further visualize the formation of the tubes at each stage of assembly, as each block is tagged with a fluorescent compound that serves as a beacon. We can then count the number of blocks incorporated in each tube as it is constructed.”

This new technique was made possible by the development in recent years of single-molecule microscopy, which enables scientists to peer into the nano-world by turning the fluorescence of individual molecules on and off. (That groundbreaking work won three U.S.- and German-based scientists the 2014 Nobel Prize in Chemistry.)

Hariri’s research is jointly supervised by chemistry professors Gonzalo Cosa and Hanadi Sleiman, who co-authored the new study. Cosa’s research group specializes in single-molecule fluorescence techniques, while Sleiman’s uses DNA chemistry to design new materials for drug delivery and diagnostic tools.

The custom-built assembly technique developed through this collaboration “gives us the ability to monitor the nanotubes as we’re building them, and see their structure, robustness and morphology,” Cosa said.

“We wanted to control the nanotubes’ lengths and features one-by-one,” said Sleiman, who holds the Canada Research Chair in DNA Nanoscience. The resulting “designer nanotubes,” she adds, promise to be far cheaper to produce on a large scale than those created with so-called DNA origami, another innovative technique for using DNA as a nanoscale construction material.

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

Stepwise growth of surface-grafted DNA nanotubes visualized at the single-molecule level by Amani A. Hariri, Graham D. Hamblin, Yasser Gidi, Hanadi F. Sleiman & Gonzalo Cosa. Nature Chemistry (2015) doi:10.1038/nchem.2184 Published online 23 February 2015

This article is behind a paywall.

Aptamers and theranostics (theragnostics)

A popular concept in some circles, theranostics (sometimes called theragnostics) is a conflation of the words ‘therapeutics’ and ‘diagnostics’. A Feb. 17, 2015 news item on Nanowerk features the use of aptamers as theranostic agents,

Aptamers are composed of short RNA or single-stranded DNA sequences that, when folded into their unique 3D conformation, can bind to their targets with high specifi city and affinity. Although functionally similar to protein antibodies, oligonucleotide aptamers offer several advantages over protein antibodies in biomedical and clinical applications.

Through the enhanced permeability and retention effect, nanomedicines can improve the therapeutic index of a treatment and reduce side effects by enhancing accumulation at the disease site. However, this targets tumors passively and, thus, may not be ideal for targeted therapy.

To construct ligand-directed “active targeting” nanobased delivery systems, aptamer-equipped nanomedicines have been tested for in vitro diagnosis, in vivo imaging, targeted cancer therapy, theranostic approaches, sub-cellular molecule detection, food safety, and environmental monitoring.

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

Aptamers and Their Applications in Nanomedicine by Hongguang Sun and Youli Zu. Small DOI: 10.1002/smll.201403073 Article first published online: 11 FEB 2015

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Here’s an illustration of the theranostic concept,

© Wiley

© Wiley

I have a bit more about aptamers in an Oct. 25, 2011 post featuring an interview with professor Maria DeRosa at the University of Ottawa.

A bio-inspired robotic sock from Singapore’s National University

Should you ever be confined to a bed over a long period of time or find yourself unable to move your legs at will, this robotic sock could help you avoid blood clots according to a Feb. 10, 2015 National University of Singapore news release (also on EurekAlert but dated Feb. 13, 2015),

Patients who are bedridden or unable to move their legs are often at risk of developing Deep Vein Thrombosis (DVT), a potentially life-threatening condition caused by blood clots forming along the lower extremity veins of the legs. A team of researchers from the National University of Singapore’s (NUS) Yong Loo Lin School of Medicine and Faculty of Engineering has invented a novel sock that can help prevent DVT and improve survival rates of patients.

Equipped with soft actuators that mimic the tentacle movements of corals, the robotic sock emulates natural lower leg muscle contractions in the wearer’s leg, thereby promoting blood circulation throughout the wearer’s body. In addition, the novel device can potentially optimise therapy sessions and enable the patient’s lower leg movements to be monitored to improve therapy outcomes.

The invention is created by Assistant Professor Lim Jeong Hoon from the NUS Department of Medicine, as well as Assistant Professor Raye Yeow Chen Hua and first-year PhD candidate Mr Low Fanzhe of the NUS Department of Biomedical Engineering.

The news release goes on to contrast this new technique with the pharmacological and other methods currently in use,

Current approaches to prevent DVT include pharmacological methods which involve using anti-coagulation drugs to prevent blood from clotting, and mechanical methods that involve the use of compressive stimulations to assist blood flow.

While pharmacological methods are competent in preventing DVT, there is a primary detrimental side effect – there is higher risk of excessive bleeding which can lead to death, especially for patients who suffered hemorrhagic stroke. On the other hand, current mechanical methods such as the use of compression stockings have not demonstrated significant reduction in DVT risk.

In the course of exploring an effective solution that can prevent DVT, Asst Prof Lim, who is a rehabilitation clinician, was inspired by the natural role of the human ankle muscles in facilitating venous blood flow back to the heart. He worked with Asst Prof Yeow and Mr Low to derive a method that can perform this function for patients who are bedridden or unable to move their legs.

The team turned to nature for inspiration to develop a device that is akin to human ankle movements. They found similarities in the elegant structural design of the coral tentacle, which can extend to grab food and contract to bring the food closer for consumption, and invented soft actuators that mimic this “push and pull” mechanism.

By integrating the actuators with a sock and the use of a programmable pneumatic pump-valve control system, the invention is able to create the desired robot-assisted ankle joint motions to facilitate blood flow in the leg.

Explaining the choice of materials, Mr Low said, “We chose to use only soft components and actuators to increase patient comfort during use, hence minimising the risk of injury from excessive mechanical forces. Compression stockings are currently used in the hospital wards, so it makes sense to use a similar sock-based approach to provide comfort and minimise bulk on the ankle and foot.”

The sock complements conventional ankle therapy exercises that therapists perform on patients, thereby optimising therapy time and productivity. In addition, the sock can be worn for prolonged durations to provide robot-assisted therapy, on top of the therapist-assisted sessions. The sock is also embedded with sensors to track the ankle joint angle, allowing the patient’s ankle motion to be monitored for better treatment.

Said Asst Prof Yeow, “Given its compact size, modular design and ease of use, the soft robotic sock can be adopted in hospital wards and rehabilitation centres for on-bed applications to prevent DVT among stroke patients or even at home for bedridden patients. By reducing the risk of DVT using this device, we hope to improve survival rates of these patients.”

The team does not seem to have published any papers about this work although there are plans for clinical trials and commercialization (from the news release),

To further investigate the effectiveness of the robotic sock, Asst Prof Lim, Asst Prof Yeow and Mr Low will be conducting pilot clinical trials with about 30 patients at the National University Hospital over six months, starting March 2015. They hope that the pilot clinical trials will help them to obtain patient and clinical feedback to further improve the design and capabilities of the device.

The team intends to conduct trials across different local hospitals for better evaluation, and they also hope to commercialise the device in future.

The researchers have provided an image of the sock on a ‘patient’,

 Caption: NUS researchers (from right to left) Assistant Professor Raye Yeow, Mr Low Fanzhe and Dr Liu Yuchun demonstrating the novel bio-inspired robotic sock. Credit: National University of Singapore


Caption: NUS researchers (from right to left) Assistant Professor Raye Yeow, Mr Low Fanzhe and Dr Liu Yuchun demonstrating the novel bio-inspired robotic sock.
Credit: National University of Singapore

Gold nanotubes could be used in cancer therapies

Where nanotubes are concerned I don’t often see mention of any type other than ‘carbon’ nanotubes so, this Feb. 12, 2015 nanomedicine news item on ScienceDaily featuring ‘gold’ nanotubes caught my attention,

Scientists have shown that gold nanotubes have many applications in fighting cancer: internal nanoprobes for high-resolution imaging; drug delivery vehicles; and agents for destroying cancer cells.

The study, published today in the journal Advanced Functional Materials, details the first successful demonstration of the biomedical use of gold nanotubes in a mouse model of human cancer.

A Feb. 13, 2015 University of Leeds press release, which originated the news item despite what the publication date suggests, describes the research in more detail (Note: Links have been removed),

Study lead author Dr Sunjie Ye, who is based in both the School of Physics and Astronomy and the Leeds Institute for Biomedical and Clinical Sciences at the University of Leeds, said:  “High recurrence rates of tumours after surgical removal remain a formidable challenge in cancer therapy. Chemo- or radiotherapy is often given following surgery to prevent this, but these treatments cause serious side effects.

Gold nanotubes – that is, gold nanoparticles with tubular structures that resemble tiny drinking straws – have the potential to enhance the efficacy of these conventional treatments by integrating diagnosis and therapy in one single system.”

The researchers say that a new technique to control the length of nanotubes underpins the research. By controlling the length, the researchers were able to produce gold nanotubes with the right dimensions to absorb a type of light called ‘near infrared’.

The study’s corresponding author Professor Steve Evans, from the School of Physics and Astronomy at the University of Leeds, said: “Human tissue is transparent for certain frequencies of light – in the red/infrared region. This is why parts of your hand appear red when a torch is shone through it.

“When the gold nanotubes travel through the body, if light of the right frequency is shone on them they absorb the light. This light energy is converted to heat, rather like the warmth generated by the Sun on skin. Using a pulsed laser beam, we were able to rapidly raise the temperature in the vicinity of the nanotubes so that it was high enough to destroy cancer cells.”

In cell-based studies, by adjusting the brightness of the laser pulse, the researchers say they were able to control whether the gold nanotubes were in cancer-destruction mode, or ready to image tumours.

In order to see the gold nanotubes in the body, the researchers used a new type of  imaging technique called ‘multispectral optoacoustic tomography’ (MSOT) to detect the gold nanotubes in mice, in which gold nanotubes had been injected intravenously. It is the first biomedical application of gold nanotubes within a living organism. It was also shown that gold nanotubes were excreted from the body and therefore are unlikely to cause problems in terms of toxicity, an important consideration when developing nanoparticles for clinical use.

Study co-author Dr James McLaughlan, from the School of Electronic & Electrical Engineering at the University of Leeds, said: “This is the first demonstration of the production, and use for imaging and cancer therapy, of gold nanotubes that strongly absorb light within the ‘optical window’ of biological tissue.

“The nanotubes can be tumour-targeted and have a central ‘hollow’ core that can be loaded with a therapeutic payload. This combination of targeting and localised release of a therapeutic agent could, in this age of personalised medicine, be used to identify and treat cancer with minimal toxicity to patients.”

The use of gold nanotubes in imaging and other biomedical applications is currently progressing through trial stages towards early clinical studies.

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

Engineering Gold Nanotubes with Controlled Length and Near-Infrared Absorption for Theranostic Applications by Sunjie Ye, Gemma Marston, James R. McLaughlan, Daniel O. Sigle, Nicola Ingram, Steven Freear, Jeremy J. Baumberg, Richard J. Bushby, Alexander F. Markham, Kevin Critchley, Patricia Louise Coletta, and Stephen D. Evans. Advanced Functional Materials DOI: 10.1002/adfm.201404358 Article first published online: 12 FEB 2015

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Fish skin for wound healing

A Feb. 11, 2015 news item on Nanowerk features Chinese research on tilapia fish skin and possible applications for wound healing (Note: A link has been removed),

With a low price tag and mild flavor, tilapia has become a staple dinnertime fish for many Americans. Now it could have another use: helping to heal our wounds. In the journal ACS Applied Materials & Interfaces (“Development of Biomimetic Tilapia Collagen Nanofibers for Skin Regeneration through Inducing Keratinocytes Differentiation and Collagen Synthesis of Dermal Fibroblasts”), scientists have shown that a protein found in this fish can promote skin repair in rats without an immune reaction, suggesting possible future use for human patients.

A Feb. 11, 2015 American Chemical Society (ACS) news release, which originated the news item, provides a few more details about the work,

Jiao Sun, Xiumei Mo and colleagues explain that applying collagen — a major structural protein in animals — to wounds can help encourage skin to heal faster.  But when the protein dressing comes from mammals such as cows and pigs, it has the potential to transmit conditions such as foot-and-mouth disease. Searching for an alternative source of collagen, scientists recently turned to the ocean. Sun’s team wanted to test fish collagen’s potential as a more benign wound treatment.

The researchers developed nanofibers from tilapia collagen and used them to cover skin wounds on rats. The rats with the nanofiber dressing healed faster than those without it. In addition, lab tests on cells suggested that the fish collagen was not likely to cause an immune reaction. The researchers conclude that it could be a good candidate to develop for clinical use.

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

Development of Biomimetic Tilapia Collagen Nanofibers for Skin Regeneration through Inducing Keratinocytes Differentiation and Collagen Synthesis of Dermal Fibroblasts by Tian Zhou, Nanping Wang, Yang Xue, Tingting Ding, Xin Liu, Xiumei Mo, and Jiao Sun. ACS Appl. Mater. Interfaces, 2015, 7 (5), pp 3253–3262 DOI: 10.1021/am507990m Publication Date (Web): January 19, 2015

Copyright © 2015 American Chemical Society

This article is behind a paywall.

Nanoscale antioxidants

A Feb. 10, 2015 news item on Azonano features injectable nanoparticles that act as antioxidants useful in case of injury, in particular, brain injury,

Injectable nanoparticles that could protect an injured person from further damage due to oxidative stress have proven to be astoundingly effective in tests to study their mechanism.

Scientists at Rice University, Baylor College of Medicine and the University of Texas Health Science Center at Houston (UTHealth) Medical School designed methods to validate their 2012 discovery that combined polyethylene glycol-hydrophilic carbon clusters — known as PEG-HCCs — could quickly stem the process of overoxidation that can cause damage in the minutes and hours after an injury.

A Feb. 9, 2015 Rice University news release (also on EurekAlert), which originated the news item, describe the benefits in more detail,

The tests revealed a single nanoparticle can quickly catalyze the neutralization of thousands of damaging reactive oxygen species molecules that are overexpressed by the body’s cells in response to an injury and turn the molecules into oxygen. These reactive species can damage cells and cause mutations, but PEG-HCCs appear to have an enormous capacity to turn them into less-reactive substances.

The researchers hope an injection of PEG-HCCs as soon as possible after an injury, such as traumatic brain injury or stroke, can mitigate further brain damage by restoring normal oxygen levels to the brain’s sensitive circulatory system.

“Effectively, they bring the level of reactive oxygen species back to normal almost instantly,” said Rice chemist James Tour. “This could be a useful tool for emergency responders who need to quickly stabilize an accident or heart attack victim or to treat soldiers in the field of battle.” Tour led the new study with neurologist Thomas Kent of Baylor College of Medicine and biochemist Ah-Lim Tsai of UTHealth.

The news release goes on to describe the antioxidant particles and previous research,

PEG-HCCs are about 3 nanometers wide and 30 to 40 nanometers long and contain from 2,000 to 5,000 carbon atoms. In tests, an individual PEG-HCC nanoparticle can catalyze the conversion of 20,000 to a million reactive oxygen species molecules per second into molecular oxygen, which damaged tissues need, and hydrogen peroxide while quenching reactive intermediates.

Tour and Kent led the earlier research that determined an infusion of nontoxic PEG-HCCs may quickly stabilize blood flow in the brain and protect against reactive oxygen species molecules overexpressed by cells during a medical trauma, especially when accompanied by massive blood loss.

Their research targeted traumatic brain injuries, after which cells release an excessive amount of the reactive oxygen species known as a superoxide into the blood. These toxic free radicals are molecules with one unpaired electron that the immune system uses to kill invading microorganisms. In small concentrations, they contribute to a cell’s normal energy regulation. Generally, they are kept in check by superoxide dismutase, an enzyme that neutralizes superoxides.

But even mild traumas can release enough superoxides to overwhelm the brain’s natural defenses. In turn, superoxides can form such other reactive oxygen species as peroxynitrite that cause further damage.

“The current research shows PEG-HCCs work catalytically, extremely rapidly and with an enormous capacity to neutralize thousands upon thousands of the deleterious molecules, particularly superoxide and hydroxyl radicals that destroy normal tissue when left unregulated,” Tour said.

“This will be important not only in traumatic brain injury and stroke treatment, but for many acute injuries of any organ or tissue and in medical procedures such as organ transplantation,” he said. “Anytime tissue is stressed and thereby oxygen-starved, superoxide can form to further attack the surrounding good tissue.”

These details about the research are also noted in the news release,

The researchers used an electron paramagnetic resonance spectroscopy technique that gets direct structure and rate information for superoxide radicals by counting unpaired electrons in the presence or absence of PEG-HCC antioxidants. Another test with an oxygen-sensing electrode, peroxidase and a red dye confirmed the particles’ ability to catalyze superoxide conversion.

“In sharp contrast to the well-known superoxide dismutase, PEG-HCC is not a protein and does not have metal to serve the catalytic role,” Tsai said. “The efficient catalytic turnover could be due to its more ‘planar,’ highly conjugated carbon core.”

The tests showed the number of superoxides consumed far surpassed the number of possible PEG-HCC bonding sites. The researchers found the particles have no effect on important nitric oxides that keep blood vessels dilated and aid neurotransmission and cell protection, nor was the efficiency sensitive to pH changes.

“PEG-HCCs have enormous capacity to convert superoxide to oxygen and the ability to quench reactive intermediates while not affecting nitric oxide molecules that are beneficial in normal amounts,” Kent said. “So they hold a unique place in our potential armamentarium against a range of diseases that involve loss of oxygen and damaging levels of free radicals.”

The study also determined PEG-HCCs remain stable, as batches up to 3 months old performed as good as new.

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

Highly efficient conversion of superoxide to oxygen using hydrophilic carbon clusters by Errol L. G. Samuel, Daniela C. Marcano, Vladimir Berka, Brittany R. Bitner, Gang Wu, Austin Potter, Roderic H. Fabian, Robia G. Pautler, Thomas A. Kent, Ah-Lim Tsai, and James M. Tour. Published online before print February 9, 2015, doi: 10.1073/pnas.1417047112 PNAS February 9, 2015

This paper is behind a paywall.

From monitoring glucose in kidneys to climate change in trees

That headline is almost poetic but I admit It’s a bit of a stretch rhymewise, kidneys/trees. In any event, a Feb. 6, 2015 news item on Azonano describes research into monitoring the effects of climate change on trees,

Serving as a testament to the far-reaching impact of Governor Andrew M. Cuomo’s commitment to maintaining New York State’s global leadership in nanotechnology innovation, SUNY Polytechnic Institute’s Colleges of Nanoscale Science and Engineering (SUNY Poly CNSE) today announced the National Science Foundation (NSF) has awarded $837,000 to support development of a first of its kind nanoscale sensor to monitor the effects of climate change on trees.

A Feb. 5, 2015 SUNY Poly CNSE news release, which originated the news item, provides more details including information about the sensor’s link to measuring glucose in kidneys,

The NSF grant was generated through the Instrument Development for Biological Research (IDBR) program, which provides funds to develop new classes of devices for bio-related research. The NANAPHID, a novel aphid-like nanosensor, will provide real-time measurements of carbohydrates in live plant tissue. Carbohydrate levels in trees are directly connected to plant productivity, such as maple sap production and survival. The NANAPHID will enable researchers to determine the effects of a variety of environmental changes including temperature, precipitation, carbon dioxide, soil acidity, pests and pathogens. The nanosensor can also provide real-time monitoring of sugar concentration levels, which are of signficant importance in maple syrup production and apple and grape farming.

“The technology for the NANAPHID is rooted in a nanoscale sensor SUNY Poly CNSE developed to monitor glucose levels in human kidneys being prepared for transplant. Our team determined that certain adjustments would enable the sensor to provide similar monitoring for plants, and provide a critical insight to the effects of climate change on the environment,” said Dr. James Castracane, professor and head of the Nanobioscience Constellation at SUNY Polytechnic Institute. “This is a perfect example of the cycle of innovation made possible through the ongoing nanotechnology research and development at SUNY Poly CNSE’s NanoTech Complex.”

“This new sensor will be used in several field experiments on measuring sensitivity of boreal forest to climate warming. Questions about forest response to rising air and soil temperatures are extremely important for forecasting future atmospheric carbon dioxide levels, climate change and forest health,” said Dr. Andrei Lapenas, principal investigator and associate professor of climatology at the University at Albany. “At the same time, we already see some potential commercial application for NANAPHID-type sensors in agriculture, food industry and other fields. Our collaboration with SUNY Poly CNSE has been extremely productive and I look forward to continuing our work together.”

The NANAPHID project began in 2014 with a $135,000 SUNY Research Foundation Network of Excellence grant. SUNY Poly CNSE will receive $400,000 of the NSF award for the manufacturing aspects of the sensor array development and testing. The remaining funds will be shared between Dr. Lapenas and researchers Dr. Ruth Yanai (ESF), Dr. Thomas Horton (ESF), and Dr. Pamela Templer (Boston University) for data collection and analysis.

“With current technology, analyzing carbohydrates in plant tissues requires hours in the lab or more than $100 a sample if you want to send them out. And you can’t sample the same tissue twice, the sample is destroyed in the analysis,” said Dr. Yanai. “The implantable device will be cheap to produce and will provide continuous monitoring of sugar concentrations, which is orders of magnitude better in both cost and in the information provided. Research questions we never dreamed of asking before will become possible, like tracking changes in photosynthate over the course of a day or along the stem of a plant, because it’s a nondestructive assay.”

“I see incredible promise for the NANAPHID device in plant ecology. We can use the sensors at the root tip where plants give sugars to symbiotic fungi in exchange for soil nutrients,” said Dr. Horton. “Some fungi are believed to be significant carbon sinks because they produce extensive fungal networks in soils and we can use the sensors to compare the allocation of photosynthate to roots colonized by these fungi versus the allocation to less carbon demanding fungi. Further, the vast majority of these symbiotic fungi cannot be cultured in lab. These sensors will provide valuable insights into plant-microbe interactions under field conditions.”

“The creation of this new sensor will make understanding the effects of a variety of environmental changes, including climate change, on the health and productivity of forests much easier to measure,” said Dr. Templer. “For the first time, we will be able to measure concentrations of carbohydrates in living trees continuously and in real-time, expanding our ability to examine controls on photosynthesis, sap flow, carbon sequestration and other processes in forest ecosystems.”

Fascinating, eh? I wonder who made the connection between human kidneys and plants and how that person made the connection.

The quantum chemistry of nanomedicines

A Jan. 29, 2015 news item on Nanowerk provides an overview of the impact quantum chemical reactions may have on nanomedicines. Intriguingly, this line of query started with computations of white dwarf stars,

Quantum chemical calculations have been used to solve big mysteries in space. Soon the same calculations may be used to produce tomorrow’s cancer drugs.

Some years ago research scientists at the University of Oslo in Norway were able to show that the chemical bonding in the magnetic fields of small, compact stars, so-called white dwarf stars, is different from that on Earth. Their calculations pointed to a completely new bonding mechanism between two hydrogen atoms. The news attracted great attention in the media. The discovery, which in fact was made before astrophysicists themselves observed the first hydrogen molecules in white dwarf stars, was made by UiO’s Centre for Theoretical and Computational Chemistry. They based their work on accurate quantum chemical calculations of what happens when atoms and molecules are exposed to extreme conditions.

A Jan. 29, 2015 University of Oslo press release by Yngve Vogt, which originated the news item, offers a substantive description of molecules, electrons, and more for those of us whose last chemistry class is lost in the mists of time,

The research team is headed by Professor Trygve Helgaker, who for the last thirty years has taken the international lead on the design of a computer system for calculating quantum chemical reactions in molecules.

Quantum chemical calculations are needed to explain what happens to the electrons’ trajectories within a molecule.

Consider what happens when UV radiation sends energy-rich photons into your cells. This increases the energy level of the molecules. The outcome may well be that some of the molecules break up. This is exactly what happens when you sun-bathe.

“The extra energy will affect the behaviour of electrons and can destroy the chemical bonding within the molecule. This can only be explained by quantum chemistry. The quantum chemical models are used to produce a picture of the forces and tensions at play between the atoms and the electrons of a molecule, and of what is required for a molecule to dissociate,” says Trygve Helgaker.

The absurd world of the electrons

The quantum chemical calculations solve the Schrödinger equation for molecules. This equation is fundamental to all chemistry and describes the whereabouts of all electrons within a molecule. But here we need to pay attention, for things are really rather more complicated than that. Your high school physics teacher will have told you that electrons circle the atom. Things are not that simple, though, in the world of quantum physics. Electrons are not only particles, but waves as well. The electrons can be in many places at the same time. It’s impossible to keep track of their position. However, there is hope. Quantum chemical models describe the electrons’ statistical positions. In other words, they can establish the probable location of each electron.

The results of a quantum chemical calculation are often more accurate than what is achievable experimentally.

Among other things, the quantum chemical calculations can be used to predict chemical reactions. This means that the chemists will no longer have to rely on guesstimates in the lab. It is also possible to use quantum chemical calculations in order to understand what happens in experiments.

Enormous calculations

The calculations are very demanding.

“The Schrödinger equation is a highly complicated, partial differential equation, which cannot be accurately solved. Instead, we need to make do with heavy simulations”, says researcher Simen Kvaal.

The computations are so demanding that the scientists use one of the University’s fastest supercomputers.

“We are constantly stretching the boundaries of what is possible. We are restricted by the available machine capacity,” explains Helgaker.

Ten years ago it took two weeks to carry out the calculations for a molecule with 140 atoms. Now it can be done in two minutes.

“That’s 20,000 times faster than ten years ago. The computation process is now running 200 times faster because the computers have been doubling their speed every eighteen months. And the process is a further 100 times faster because the software has been undergoing constant improvement,” says senior engineer Simen Reine.

This year the research group has used 40 million CPU hours, of which twelve million were on the University’s supercomputer, which is fitted with ten thousand parallel processors. This allows ten thousand CPU hours to be over and done with in 60 minutes.

“We will always fill the computer’s free capacity. The higher the computational capacity, the bigger and more reliable the calculations.”

Thanks to ever faster computers, the quantum chemists are able to study ever larger molecules.

Today, it’s routine to carry out a quantum chemical calculation of what happens within a molecule of up to 400 atoms. By using simplified models it is possible to study molecules with several thousand atoms. This does, however, mean that some of the effects within the molecule are not being described in detail.

The researchers are now getting close to a level which enables them to study the quantum mechanics of living cells.

“This is exciting. The molecules of living cells may contain many hundred thousand atoms, but there is no need to describe the entire molecule using quantum mechanical principles. Consequently, we are already at a stage when we can help solve biological problems.”

There’s more from the press release which describes how this work could be applied in the future,

Hunting for the electrons of the insulin molecule

The chemists are thus able to combine sophisticated models with simpler ones. “This will always be a matter of what level of precision and detail you require. The optimal approach would have been to use the Schrödinger equation for everything.”

By way of compromise they can give a detailed description of every electron in some parts of the model, while in other parts they are only looking at average numbers.

Simen Reine has been using the team’s computer program, while working with Aarhus University [Finland], on a study of the insulin molecule. An insulin molecule consists of 782 atoms and 3,500 electrons.

“All electrons repel each other, while at the same time being pulled towards the atomic nuclei. The nuclei also repel each other. Nevertheless, the molecule remains stable. In order to study a molecule to a high level of precision, we therefore need to consider how all of the electrons move relative to one another. Such calculations are referred to as correlated and are very reliable.”

A complete correlated calculation of the insulin molecule takes nearly half a million CPU hours. If they were given the opportunity to run the program on the entire University’s supercomputer, the calculations would theoretically take two days.

“In ten years, we’ll be able to make these calculations in two minutes.”

Medically important

“Quantum chemical calculations can help describe phenomena at a level that may be difficult to access experimentally, but may also provide support for interpreting and planning experiments. Today, the calculations will be put to best use within the fields of molecular biology and biochemistry,” says Knut Fægri [vice-rector at the University of Oslo].

“Quantum chemistry is a fundamental theory which is important for explaining molecular events, which is why it is essential to our understanding of biological systems,” says [Associate Professor] Michele Cascella.

By way of an example, he refers to the analysis of enzymes. Enzymes are molecular catalysts that boost the chemical reactions within our cells.

Cascella also points to nanomedicines, which are drugs tasked with distributing medicine round our bodies in a much more accurate fashion.

“In nanomedicine we need to understand physical phenomena on a nano scale, forming as correct a picture as possible of molecular phenomena. In this context, quantum chemical calculations are important,” explains Michele Cascella.

Proteins and enzymes

Professor K. Kristoffer Andersson at the Department of Biosciences uses the simpler form of quantum chemical calculations to study the details of protein structures and the chemical atomic and electronic functions of enzymes.

“It is important to understand the chemical reaction mechanism, and how enzymes and proteins work. Quantum chemical calculations will teach us more about how proteins go about their tasks, step by step. We can also use the calculations to look at activation energy, i.e. how much energy is required to reach a certain state. It is therefore important to understand the chemical reaction patterns in biological molecules in order to develop new drugs,” says Andersson.

His research will also be useful in the search for cancer drugs. He studies radicals, which may be important to cancer. Among other things, he is looking at the metal ions function in proteins. These are ions with a large number of protons, neutrons and electrons.

Photosynthesis

Professor Einar Uggerud at the Department of Chemistry has uncovered an entirely new form of chemical bonding through sophisticated experiments and quantum chemical calculations.

Working with research fellow Glenn Miller, Professor Uggerud has found an unusually fragile key molecule, in a kite-shaped structure, consisting of magnesium, carbon and oxygen. The molecule may provide a new understanding of photosynthesis. Photosynthesis, which forms the basis for all life, converts CO2 into sugar molecules.

The molecule reacts so fast with water and other molecules that it has only been possible to study in isolation from other molecules, in a vacuum chamber.

“Time will tell whether the molecule really has an important connection with photosynthesis,” says Einar Uggerud.

I’m delighted with this explanation as it corrects my understanding of chemical bonds and helps me to better understand computational chemistry. Thank you University of Oslo and Yngve Vogt.

Finally, here’s a representation of an insulin molecule as understood by quantum computation,

QuantumInsulinMolecule

INSULIN: Working with Aarhus University, Simen Reine has calculated the tensions between the electrons and atoms of an insulin molecule. An insulin molecule consists of 782 atoms and 3,500 electrons. Illustration: Simen Reine-UiO