Category Archives: medicine

Maple syrup as an antibiotic helper?

This maple syrup research is from McGill University in Montréal, Québec (from an April 16, 2015 McGill University news release; also on EurekAlert),

A concentrated extract of maple syrup makes disease-causing bacteria more susceptible to antibiotics, according to laboratory experiments by researchers at McGill University.

The findings, which will be published in the journal Applied and Environmental Microbiology, suggest that combining maple syrup extract with common antibiotics could increase the microbes’ susceptibility, leading to lower antibiotic usage. Overuse of antibiotics fuels the emergence of drug-resistant bacteria, which has become a major public-health concern worldwide.

Prof. Nathalie Tufenkji’s research team in McGill’s Department of Chemical Engineering prepared a concentrated extract of maple syrup that consists mainly of phenolic compounds. Maple syrup, made by concentrating the sap from North American maple trees, is a rich source of phenolic compounds.

The researchers tested the extract’s effect in the laboratory on infection-causing strains of certain bacteria, including E. coli and Proteus mirabilis (a common cause of urinary tract infection). By itself, the extract was mildly effective in combating bacteria. But the maple syrup extract was particularly effective when applied in combination with antibiotics. The extract also acted synergistically with antibiotics in destroying resistant communities of bacteria known as biofilms, which are common in difficult-to-treat infections, such as catheter-associated urinary tract infections.

“We would have to do in vivo tests, and eventually clinical trials, before we can say what the effect would be in humans,” Tufenkji says. “But the findings suggest a potentially simple and effective approach for reducing antibiotic usage. I could see maple syrup extract being incorporated eventually, for example, into the capsules of antibiotics.”

The scientists also found that the extract affects the gene expression of the bacteria, by repressing a number of genes linked with antibiotic resistance and virulence.

All maple syrup samples used in the study were purchased at local markets in Montreal, then frozen until the beginning of each experiment, which involved a series of steps to produce the phenolic-rich extract.

Tufenkji, who holds the Canada Research Chair in Biocolloids and Surfaces, has also studied the potential for cranberry derivatives to fight infection-causing bacteria. The new study is co-authored by postdoctoral fellows Vimal Maisuria and Zeinab Hosseinidoust.

Here’s a link to and a citation for the paper which at this time (April 24, 2014) is not yet published,,

Polyphenolic Extract from Maple Syrup Potentiates Antibiotic Susceptibility and Reduces Biofilm Formation of Pathogenic Bacteria by Vimal B. Maisuria, Zeinab Hosseinidoust, and Nathalie Tufenkji. doi: 10.1128/AEM.00239-15 AEM [Applied and Environmental Microbiology].00239-15

My guess is that this paper will be behind a paywall. Fear not! There is a very informative 3 mins. or so video,

I particularly appreciated the maple leaf-shaped glass container (still full) which is shown prominently when the researcher mentions purchasing the syrup from local markets.

Reversing Parkinson’s type symptoms in rats

Indian scientists have developed a technique for delivering drugs that could reverse Parkinson-like symptoms according to an April 22, 2015 news item on Nanowerk (Note: A link has been removed),

As baby boomers age, the number of people diagnosed with Parkinson’s disease is expected to increase. Patients who develop this disease usually start experiencing symptoms around age 60 or older. Currently, there’s no cure, but scientists are reporting a novel approach that reversed Parkinson’s-like symptoms in rats.

Their results, published in the journal ACS Nano (“Trans-Blood Brain Barrier Delivery of Dopamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Rats”), could one day lead to a new therapy for human patients.

An April 22, 2015 American Chemical Society press pac news release (also on EurekAlert), which originated the news item, describes the problem the researchers were solving (Note: Links have been removed),

Rajnish Kumar Chaturvedi, Kavita Seth, Kailash Chand Gupta and colleagues from the CSIR-Indian Institute of Toxicology Research note that among other issues, people with Parkinson’s lack dopamine in the brain. Dopamine is a chemical messenger that helps nerve cells communicate with each other and is involved in normal body movements. Reduced levels cause the shaking and mobility problems associated with Parkinson’s. Symptoms can be relieved in animal models of the disease by infusing the compound into their brains. But researchers haven’t yet figured out how to safely deliver dopamine directly to the human brain, which is protected by something called the blood-brain barrier that keeps out pathogens, as well as many medicines. Chaturvedi and Gupta’s team wanted to find a way to overcome this challenge.

The researchers packaged dopamine in biodegradable nanoparticles that have been used to deliver other therapeutic drugs to the brain. The resulting nanoparticles successfully crossed the blood-brain barrier in rats, released its dopamine payload over several days and reversed the rodents’ movement problems without causing side effects.

The authors acknowledge funding from the Indian Department of Science and Technology as Woman Scientist and Ramanna Fellow Grant, and the Council of Scientific and Industrial Research (India).

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

Trans-Blood Brain Barrier Delivery of Dopamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Rats by Richa Pahuja, Kavita Seth, Anshi Shukla, Rajendra Kumar Shukla, Priyanka Bhatnagar, Lalit Kumar Singh Chauhan, Prem Narain Saxena, Jharna Arun, Bhushan Pradosh Chaudhari, Devendra Kumar Patel, Sheelendra Pratap Singh, Rakesh Shukla, Vinay Kumar Khanna, Pradeep Kumar, Rajnish Kumar Chaturvedi, and Kailash Chand Gupta. ACS Nano, Article ASAP DOI: 10.1021/nn506408v Publication Date (Web): March 31, 2015
Copyright © 2015 American Chemical Society

This paper is open access.

Another recent example of breaching the blood-brain barrier, coincidentally, in rats, can be found in my Dec. 24, 2014 titled: Gelatin nanoparticles for drug delivery after a stroke. Scientists are also trying to figure out the the blood-brain barrier operates in the first place as per this April 22, 2015 University of Pennsylvania news release on EurekAlert titled, Penn Vet, Montreal and McGill researchers show how blood-brain barrier is maintained (University of Pennsylvania School of Veterinary Medicine, University of Montreal or Université de Montréal, and McGill University). You can find out more about CSIR-Indian Institute of Toxicology Research here.

Electronic organic micropump for direct drug delivery to the brain

I can understand the appeal but have some questions about this micropump in the brain concept. First, here’s more about the research from an April 16, 2015 news item on Nanowerk,

Many potentially efficient drugs have been created to treat neurological disorders, but they cannot be used in practice. Typically, for a condition such as epilepsy, it is essential to act at exactly the right time and place in the brain. For this reason, the team of researchers led by Christophe Bernard at Inserm Unit 1106, “Institute of Systems Neuroscience” (INS), with the help of scientists at the École des Mines de Saint-Étienne and Linköping University (Sweden) have developed an organic electronic micropump which, when combined with an anticonvulsant drug, enables localised inhibition of epileptic seizure in brain tissue in vitro.

An April 16, 2015 INSERM (Institut national de la santé et de la recherche médicale) press release on EurekAlert, which originated the news item, goes on to describe the problem the researchers are attempting to solve and their solution to it,

Drugs constitute the most widely used approach for treating brain disorders. However, many promising drugs failed during clinical testing for several reasons:

  • they are diluted in potentially toxic solutions,
  • they may themselves be toxic when they reach organs to which they were not initially directed,
  • the blood-brain barrier, which separates the brain from the blood circulation, prevents most drugs from reaching their targets in the brain,
  • drugs that succeed in penetrating the brain will act in a non-specific manner, i.e. on healthy regions of the brain, altering their functions.

Epilepsy is a typical example of a condition for which many drugs could not be commercialised because of their harmful effects, when they might have been effective for treating patients resistant to conventional treatments [1].

During an epileptic seizure, the nerve cells in a specific area of the brain are suddenly activated in an excessive manner. How can this phenomenon be controlled without affecting healthy brain regions? To answer this question, Christophe Bernard’s team, in collaboration with a team led by George Malliaras at the Georges Charpak-Provence Campus of the École des Mines of Saint-Étienne and Swedish scientists led by Magnus Berggren from Linköping University, have developed a biocompatible micropump that makes it possible to deliver therapeutic substances directly to the relevant areas of the brain.

The micropump (20 times thinner than a hair) is composed of a membrane known as “cation exchange,” i.e., it has negative ions attached to its surface. It thus attracts small positively charged molecules, whether these are ions or drugs. When an electrical current is applied to it, the flow of electrons generated projects the molecules of interest toward the target area.

To enable validation of this new technique, the researchers reproduced the hyperexcitability of epileptic neurons in mouse brains in vitro. They then injected GABA, a compound naturally produced in the brain and that inhibits neurons, into this hyperactive region using the micropump. The scientists then observed that the compound not only stopped this abnormal activity in the target region, but, most importantly, did not interfere with the functioning of the neighbouring regions.

This technology may thus resolve all the above-mentioned problems, by allowing very localised action, directly in the brain and without peripheral toxicity.

“By combining electrodes, such as those used to treat Parkinson’s disease, with this micropump, it may be possible to use this technology to treat patients with epilepsy who are resistant to conventional treatments, and those for whom the side-effects are too great,” explains Christophe Bernard, Inserm Research Director.

Based on these initial results, the researchers are now working to move on to an in vivo animal model and the possibility of combining this high-technology system with the microchip they previously developed in 2013. The device could be embedded and autonomous. The chip would be used to detect the imminent occurrence of a seizure, in order to activate the pump to inject the drug at just the right moment. It may therefore be possible to control brain activity where and when it is needed.

In addition to epilepsy, this state-of-the-art technology, combined with existing drugs, offers new opportunities for many brain diseases that remain difficult to treat at this time.

###

[1] Epilepsy in brief

This disease, which affects nearly 50 million people in the world, is the most common neurological disorder after migraine.

The neuronal dysfunctions associated with epilepsy lead to attacks with variable symptoms, from loss of consciousness to disorders of movement, sensation or mood.

Despite advances in medicine, 30% of those affected are resistant to all treatments.

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

Controlling Epileptiform Activity with Organic Electronic Ion Pumps by Adam Williamson, Jonathan Rivnay, Loïg Kergoat, Amanda Jonsson, Sahika Inal, Ilke Uguz, Marc Ferro, Anton Ivanov, Theresia Arbring-Sjöström, Daniel T. Simon, Magnus Berggren, George G. Malliaras, and Christophe Bernardi. Advanced Materials First published: 11 April 2015Full publication history DOI: 10.1002/adma.201500482

This paper is behind a paywall.

Finally, my questions. How does the pump get refilled once the drugs are used up? Do you get a warning when the drug supply is almost nil? How does that warning work? Does implanting the pump require brain surgery or is there a less intrusive fashion of placing this pump exactly where you want it to be? Once it’s been implanted, how do you find a pump  20 times thinner than a human hair?

For some reason this micropump brought back memories of working in high tech environments where developers would come up with all kinds of nifty ideas but put absolutely no thought into how these ideas might actually work once human human beings got their hands on the product. In any event, the micropump seems exciting and I hope researchers work out the kinks, implementationwise, before they’re implanted.

Electrifying DNA (deoxyribonucleic acid)

All kinds of things have electrical charges including DNA (deoxyribonucleic acid) according to an April 15, 2015 news item on Azonano,

Electrical charges not only move through wires, they also travel along lengths of DNA, the molecule of life. The property is known as charge transport.

In a new study appearing in the journal Nature Chemistry, authors, Limin Xiang, Julio Palma, Christopher Bruot and others at Arizona State University’s Biodesign Institute, explore the ways in which electrical charges move along DNA bases affixed to a pair of electrodes.

Their work reveals a new mechanism of charge transport that differs from the two recognized patterns in which charge either tunnels or hops along bases of the DNA chain.

An April 13, 2015 Arizona State University (ASU) news release (also on EurekAlert and dated April 14, 2015), which originated the news item, explains why this ‘blue sky’ research may prove important in the future,

Researchers predict that foundational work of this kind will have important implications in the design of a new generation of functional DNA-based electronic devices as well as providing new insights into health risks associated with transport-related damage to DNA.

Oxidative damage is believed to play a role in the initiation and progression of cancer. It is also implicated in neurodegenerative disorders like Alzheimer’s, Huntington’s disease and Parkinson’s disease and a range of other human afflictions.

An electron’s movements plays an important role in your body’s chemical reactions (from the news release),

The transfer of electrons is often regarded as the simplest form of chemical reaction, but nevertheless plays a critical role in a broad range of life-sustaining processes, including respiration and photosynthesis.

Charge transport can also produce negative effects on living systems, particularly through the process of oxidative stress, which causes damage to DNA and has been invoked in a broad range of diseases.

“When DNA is exposed to UV light, there’s a chance one of the bases– such as guanine–gets oxidized, meaning that it loses an electron,” Tao says. (Guanine is easier to oxidize than the other three bases, cytosine, thymine, and adenine, making it the most important base for charge transport.)

In some cases, the DNA damage is repaired when an electron migrates from another portion of the DNA strand to replace the missing one. DNA repair is a ceaseless, ongoing process, though a gradual loss of repair efficiency over time is one factor in the aging process. Oxidation randomly damages both RNA and DNA, which can interfere with normal cellular metabolism.

Radiation damage is also an issue for semiconductor devices, Tao notes–a factor that must be accounted for when electronics are exposed to high-energy particles like X rays, as in applications designed for outer space.

Researchers like Xiang and Tao hope to better understand charge transport through DNA, and the molecule provides a unique testing ground for observation. The length of a DNA molecule and its sequence of 4 nucleotides A, T, C and G can be readily modified and studies have shown that both alterations have an effect on how electrical charge moves through the molecule.

When the loss of an electron or oxidation occurs in DNA bases, a hole is left in place of the electron. This hole carries a positive charge, which can move along the DNA length under the influence of an electrical or magnetic field, just as an electron would. The movement of these positively charged holes along a stretch of DNA is the focus of the current study.

The news release goes on to describe charge transport,

Two primary mechanisms of charge transport have been examined in detail in previous research. Over short distances, an electron displays the properties of a wave, permitting it to pass straight through a DNA molecule. This process is a quantum mechanical effect known as tunneling.

Charge transport in DNA (and other molecules) over longer distances involves the process of hopping. When a charge hops from point to point along the DNA segment, it behaves classically and loses its wavelike properties. The electrical resistance is seen to increases exponentially during tunneling behavior and linearly, during hopping.

By attaching electrodes to the two ends of a DNA molecule, the researchers were able to monitor the passage of charge through the molecule, observing something new: “What we found in this particular paper is that there is an intermediate behavior,” Tao says. “It’s not exactly hopping because the electron still displays some of the wave properties.”

Instead, the holes observed in certain sequences of DNA are delocalized, spread over several base pairs. The effect is neither a linear nor exponential increase in electrical resistance but a periodic oscillation. The phenomenon was shown to be highly sequence dependent, with stacked base pairs of guanine-cytosine causing the observed oscillation.

Control experiments where G bases alternated, rather than occurring in a sequential stack, showed a linear increase in resistance with molecular length, in agreement with conventional hopping behavior.

A further property of DNA is also of importance in considering charge transport. The molecule at room temperature is not like a wire in a conventional electronic device, but rather is a highly dynamic structure, that writhes and fluctuates.

The last bit about writhing and fluctuating makes this work sound fascinating and very challenging.

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

Intermediate tunnelling–hopping regime in DNA charge transport by Limin Xiang, Julio L. Palma, Christopher Bruot, Vladimiro Mujica, Mark A. Ratner, & Nongjian Tao. Nature Chemistry 7, 221–226 (2015) doi:10.1038/nchem.2183 Published online 20 February 2015

This paper is behind a paywall.

Canada’s cannabis biotech and InMed Pharma’s nanoparticle-based drug delivery system grant

Unfortunately, there’s not much detail about the nanoparticle-based drug delivery of what I gather is a form of cannabis useful in the treatment of glaucoma in this April 16, 2015 news item on Azonano,

InMed Pharmaceuticals Inc., a clinical stage biopharmaceutical company that specializes in developing safer, more effective cannabinoid-based therapies, today announced that it has been awarded a grant to further develop the Company’s proprietary nanoparticle-based delivery system for their leading drug candidate CTI-085 for glaucoma.

An April 15, 2015 InMed Pharmaceuticals press release goes on to describe the lead researcher and her past experience, as well as, providing a ‘we’re thrilled and will do wonderful things with this money’ quote,

The Mitacs grant was awarded to Dr. Maryam Kabiri, Ph.D., a researcher with extensive experience in developing nanoparticle-based delivery system. Dr. Kabiri will be working with Prof. Vikramaditya G. Yadav, whose research focuses on metabolic & enzyme engineering and customize novel biosynthetic enzymes that can convert biomass-derived feedstock into better fuels, pharmaceuticals and value-added chemicals. In conjunction with InMed, the Mitacs grant will be utilized to develop a novel delivery system for glaucoma therapy.

Dr. Sazzad Hossain, Chief Scientific Officer, states, “We are pleased to have met the Mitacs funding criteria for the advancement of our proprietary glaucoma delivery system. Not only does this bring us closer to our goals of initiating our Phase 1 trial, but it furthers our business development strategy of having a proprietary delivery system that can be licensed with existing drugs endangered by patent expiration. This “therapy extension” strategy used by drug makers can be a valuable asset to InMed upon successful completion of the program. Additionally, the incorporation of an existing medicine into a new drug delivery system can significantly improve its performance in terms of efficacy, safety, and improved patient compliance.”

About Mitacs
Mitacs is a national, private not-for-profit organization that develops the next generation of innovators with vital scientific and business skills through a suite of unique research and training programs, such as Mitacs-Accelerate, Elevate, Step, Enterprise and Globalink. In partnership with companies, government and universities, Mitacs is supporting a new economy using Canada’s most valuable resource – its people.

For more information on Mitacs, visit www.mitacs.ca.

About InMed
InMed is a clinical stage biopharmaceutical company that specializes in developing cannabis based therapies through the Research and Development into the extensive pharmacology of cannabinoids coupled with innovative drug delivery systems. InMeds’ proprietary platform technology, product pipeline and accelerated development pathway are the fundamental value drivers of the Company.

As is becoming increasingly common, there’s a major focus on business even from Dr. Sazzad Hossain, the company’s chief scientific officer who might be expected to comment on the science. Business used to be the purview of the chief executive officer, the chief financial officer, the chief operating officer,  and/or the chief marketing officer.

I did manage to dig up a bit of information about InMed which was called Cannabis Technologies until fairly recently. Daniel Cossins in a Dec. 1, 2014 article for The Scientist describes the current ‘cannabis pharmaceutical’ scene. The dominant  player on the scene is a UK-based company, GW but InMed merits a mention,

Leading scientists were consulted, including  biotech entrepreneur Geoffrey Guy, who had  previously shown interest in developing cannabis-based medicines. The government granted Guy’s company, GW Pharmaceuticals, a license to grow cannabis plants. Guy’s idea was to generate strains rich in particular cannabinoid compounds that act on the nervous system, then test the effects of various cannabinoid combinations on MS and chronic pain. “It was a case of patient experience guiding scientific exploration,” says Stephen Wright, director of research and development at GW.

In 2010, the company announced the UK launch of its first cannabinoid-based product: Sativex, an oral spray for the treatment of MS spasticity, became the world’s first prescription medicine made from cannabis extracts. Sativex is now approved for use by MS patients in 24 countries, including France, Germany, Italy, and Australia. GW has partnered with Bayer and Novartis to market the  product. It has also signed up with the American branch of Japanese pharma company Otsuka to commercialize the drug in the U.S., where it is currently in Phase 3 clinical trials for treating MS spasticity and cancer pain. Earlier this year, GW’s share price surged when the US Food and Drug  Administration (FDA) granted orphan status to its cannabis-derived antiseizure drug Epidiolex, meaning it will be fast-tracked through clinical trials.

The company’s success is blazing a trail. In recent years, a handful of North American companies have set out on a similar path toward producing cannabis-derived pharmaceuticals. At least one company is developing candidates based on synthetic cannabinoids — of which two are already on the market in the U.S. — while several others are extracting chemical cocktails from the plant. They’re all hoping to capitalize on the anticipated growth of the cannabis pharma space by taking advantage of mounting data on the plant’s therapeutic effects.

“Frankly, we looked at GW and saw that the shift toward pharmacological development of marijuana is  already happening,” says Craig Schneider, president and CEO of InMed Pharmaceuticals (formerly Cannabis Technologies), a Vancouver-based biotech focused on pharmaceutical marijuana. “We see the likes of Otsuka, Novartis, and Eli Lilly diving into the space, and we want to be part of that.”

Cossins’ article goes on to discuss cannibinoids providing a tutorial of sorts on the topic. Meanwhile following on the business aspects of this story, Yahoo Finance  hosts a June 25, 2014 article from Accesswire, which provides some insight into the company, which was still being called Cannabis Technologies, and its GW aspirations,

 Cannabinoids are a diverse set of chemical compounds that act on cannabinoid receptors on cells that repress neurotransmitter release in the brain. While tetrahydrocannabinol (“THC”) and cannabidiol (“CBD”) are the two most popular cannabinoids, there are at least 85 different cannabinoids isolated from cannabis exhibiting various effects that could prove therapeutic.

GW Pharmaceuticals plc (GWPH), a biopharmaceutical company focused on discovering, developing, and commercializing novel therapeutics from its proprietary cannabinoid platform, has become the cannabinoid industry’s poster child with a ~$1.4 billion market capitalization and promising data from the clinic for the treatment of Dravet syndrome and Lennox-Gastaut syndrome.

In this article, we’ll take a look at another opportunity in the sector that many are calling the “junior GW” [InMed Pharma, formerly Cannabis Technologies], focused on leveraging its proprietary Cannabinoid Drug Design Platform to rapidly develop cannabinoid-based therapies.

Fully Integrated Platform Play

Cannabis Technologies Inc. (CSE:CAN) (CANLF) is a biopharmaceutical drug discovery and development company focused on cannabinoids that has been dubbed by many as the “Junior GW” in the space. By leveraging its proprietary Cannabinoid Drug Design Platform, management aims to identify new bioactive compounds within the marijuana plant that interact with certain genes.

According to Chief Science Officer Sazzad Hossain, the platform provides the bioinformatics tools necessary to isolate and identify chemical compounds in medical marijuana in months instead of years. The company plans to use the platform to isolate compounds targeting a specific disease and then outsource the early-stage research and trials to get to Phase I quickly and inexpensively.

The company’s initial focus is on the $12 billion ocular diseases market, including the $5.7 billion glaucoma market, where its CTI-085 is preparing to undergo Phase I clinical trials shortly after having completing preclinical trials. In addition to these areas, management also expressed interest in larger market places like pain and inflammation, as well as orphan diseases, cancers, and metabolic diseases.

Similar to GW Pharmaceuticals, the company also operates a breeding and cultivation division that’s responsible for creating its medicines in-house. The proprietary phyto-stock produced by the division sets the firm apart from some of its competitors that rely on third-parties to manufacture their treatments, since the fully-integrated operations are often both lower cost and greater quality.

They certainly have high business hopes for InMed Pharma. As for the science, the company has a Cannabinoid Science webpage on its site,

The majority of pharmaceutical and academic research & development being performed with cannabis revolves around the understanding of its active ingredients, the Cannabinoids

Currently there are between 80-100 cannabinoids that have been isolated from cannabis, that affect the body’s cannabinoid receptors and are responsible for unique pharmacological effects.

There are three general types of cannabinoids: herbal cannabinoids which occur uniquely in the cannabis; endogenous cannabinoids produced in the bodies of humans and animals and synthetic cannabinoids produced in the laboratory.

I was not able to find anything about the company’s nanoparticle-based delivery system on its website.

New $1 test for early stage prostate cancer more sensitive and exact than standard tests

An April 5, 2015 news item on Nanotechnology Now describes an exciting development in testing for cancer,

The simple test developed by University of Central Florida scientist Qun “Treen” Huo holds the promise of earlier detection of one of the deadliest cancers among men. It would also reduce the number of unnecessary and invasive biopsies stemming from the less precise PSA test that’s now used.

“It’s fantastic,” said Dr. Inoel Rivera, a urologic oncologist at Florida Hospital Cancer Institute, which collaborated with Huo on the recent pilot studies. “It’s a simple test. It’s much better than the test we have right now, which is the PSA, and it’s cost-effective.”

An April 3, 2015 University of Central Florida (UCF) news release by Mark Schlueb (also on EurekAlert), which originated the news item, describes the test in more detail,

When a cancerous tumor begins to develop, the body mobilizes to produce antibodies. Huo’s test detects that immune response using gold nanoparticles about 10,000 times smaller than a freckle.

When a few drops of blood serum from a finger prick are mixed with the gold nanoparticles, certain cancer biomarkers cling to the surface of the tiny particles, increasing their size and causing them to clump together.

Among researchers, gold nanoparticles are known for their extraordinary efficiency at absorbing and scattering light. Huo and her team at UCF’s NanoScience Technology Center developed a technique known as nanoparticle-enabled dynamic light scattering assay (NanoDLSay) to measure the size of the particles by analyzing the light they throw off. That size reveals whether a patient has prostate cancer and how advanced it may be.

And although it uses gold, the test is cheap. A small bottle of nanoparticles suspended in water costs about $250, and contains enough for about 2,500 tests.

“What’s different and unique about our technique is it’s a very simple process, and the material required for the test is less than $1,” Huo said. “And because it’s low-cost, we’re hoping most people can have this test in their doctor’s office. If we can catch this cancer in its early stages, the impact is going to be big.”

After lung cancer, prostate cancer is the second-leading killer cancer among men, with more than 240,000 new diagnoses and 28,000 deaths every year. The most commonly used screening tool is the PSA, but it produces so many false-positive results – leading to painful biopsies and extreme treatments – that one of its discoverers recently called it “hardly more effective than a coin toss.”

Pilot studies found Huo’s technique is significantly more exact. The test determines with 90 to 95 percent confidence that the result is not false-positive. When it comes to false-negatives, there is 50 percent confidence – not ideal, but still significantly higher than the PSA’s 20 percent – and Huo is working to improve that number.

The results of the pilot studies were published recently in ACS Applied Materials & Interfaces. Huo is also scheduled to present her findings in June at the TechConnect World Innovation Summit & Expo in suburban Washington, D.C.

Huo’s team is pursuing more extensive clinical validation studies with Florida Hospital and others, including the VA Medical Center Orlando. She hopes to complete major clinical trials and see the test being used by physicians in two to three years.

Huo also is researching her technique’s effectiveness as a screening tool for other tumors.

“Potentially, we could have a universal screening test for cancer,” she said. “Our vision is to develop an array of blood tests for early detection and diagnosis of all major cancer types, and these blood tests are all based on the same technique and same procedure.”

Huo co-founded Nano Discovery Inc., a startup company headquartered in a UCF Business Incubator, to commercialize the new diagnostic test. The company manufacturers a test device specifically for medical research and diagnostic purposes.

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

Gold Nanoparticle-Enabled Blood Test for Early Stage Cancer Detection and Risk Assessment by Tianyu Zheng, Nickisha Pierre-Pierre, Xin Yan, Qun Huo, Alvin J.O. Almodovar, Felipe Valerio, Inoel Rivera-Ramirez, Elizabeth Griffith, David D. Decker, Sixue Chen, and Ning Zhu. ACS Appl. Mater. Interfaces, 2015, 7 (12), pp 6819–6827 DOI: 10.1021/acsami.5b00371

Publication Date (Web): March 10, 2015

This paper is behind a paywall.

You can find out more about Huo’s company, Nano Discovery Inc. here.

Self-assembling nanofibres could help mitigate side effects from pain killers

The research itself is pretty exciting but even more so is the fact that it was conducted by an undergraduate student. From an April 3, 2015 news item on Azonano,

A Chemistry undergraduate at the University of York [UK] has helped to develop a new drug release gel, which may help avoid some of the side effects of painkillers such as ibuprofen and naproxen.

In a final year project, MChem undergraduate student Edward Howe, working in Professor David Smith’s research team in the Department of Chemistry at York looked for a way of eliminating the adverse side-effects associated pain-killing drugs, particularly in the stomach, and the problems, such as ulceration, this could cause patients.

A March 31, 2015 University of York press release, which originated the news item, describes the research in more detail,

Supervised by PhD student Babatunde Okesola, whose research is supported by The Wild Chemistry Scholars Fund, Edward hoped to create gels which could interact with drugs such as Naproxen, and release them at the slightly alkaline pH values found in the intestine rather than the acidic conditions in the stomach.  His aim was to both protect the pain-killing drugs and help limit some of the side effects they can cause.

The researchers created a new gel, based on small molecules which self-assemble into nanofibers which could interact with a variety of anti-inflammatory, painkiller drugs, including iburofen and naproxen. The research is published in Chemical Communications.

Specific interactions between the gel nanofibres and the drugs meant that high loadings could be achieved, and more importantly, the release of the drug could be precisely controlled.  The gels were able to release naproxen at pH 8 – the value found in the intestine, but not at lower pH values found elsewhere in the body.

Professor Smith said: “Although researchers have used gels before to try and improve the formulation of naproxen, this is the first time that a self-assembling system has been used for the job, with the advantages of directed interactions between the nanoscale delivery scaffold and the drug.  As such, this is the first time that such precise control has been achieved.”

Edward Howe said: “The research really fascinated me. The prospect of being involved in developing a method to reduce the pain of others filled me with great pride. Understanding the interactions between the gel and the painkillers was very interesting and improved my knowledge of supramolecular chemistry.”

The next step for Professor Smith’s team will involve stabilising the gel drug delivery systems in the very acidic, low pH conditions found in the stomach so that they can transit safely to the intestine before delivering naproxen just where it is needed.

Professor Smith added: “Perhaps this is something that one of next year’s undergraduate project students might solve. As a research-intensive institution, York is committed to its undergraduates carrying out cutting-edge research such as this.”

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

Self-assembled sorbitol-derived supramolecular hydrogels for the controlled encapsulation and release of active pharmaceutical ingredients by Edward J. Howe, Babatunde O. Okesola, and David K. Smith. Chem. Commun., 2015, Advance Article DOI: 10.1039/C5CC01868D First published online 31 Mar 2015

This paper is behind a paywall.

Microbubbles reform into nanoparticles after bursting

It seems researchers at the Toronto-based (Canada), Princess Margaret Cancer Centre, have developed a new theranostic tool made of microbubbles used for imaging that are then burst into nanoparticles delivering therapeutics. From a March 30, 2015 news item on phys.org,

Biomedical researchers led by Dr. Gang Zheng at Princess Margaret Cancer Centre have successfully converted microbubble technology already used in diagnostic imaging into nanoparticles that stay trapped in tumours to potentially deliver targeted, therapeutic payloads.

The discovery, published online today [March 30, 2015] in Nature Nanotechnology, details how Dr. Zheng and his research team created a new type of microbubble using a compound called porphyrin – a naturally occurring pigment in nature that harvests light.

A March 30, 2015 University Health Network news release on EurekAlert, which originated the news item, describes the laboratory research on mice,

In the lab in pre-clinical experiments, the team used low-frequency ultrasound to burst the porphyrin containing bubbles and observed that they fragmented into nanoparticles. Most importantly, the nanoparticles stayed within the tumour and could be tracked using imaging.

“Our work provides the first evidence that the microbubble reforms into nanoparticles after bursting and that it also retains its intrinsic imaging properties. We have identified a new mechanism for the delivery of nanoparticles to tumours, potentially overcoming one of the biggest translational challenges of cancer nanotechnology. In addition, we have demonstrated that imaging can be used to validate and track the delivery mechanism,” says Dr. Zheng, Senior Scientist at the Princess Margaret and also Professor of Medical Biophysics at the University of Toronto.

Conventional microbubbles, on the other hand, lose all intrinsic imaging and therapeutic properties once they burst, he says, in a blink-of-an-eye process that takes only a minute or so after bubbles are infused into the bloodstream.

“So for clinicians, harnessing microbubble to nanoparticle conversion may be a powerful new tool that enhances drug delivery to tumours, prolongs tumour visualization and enables them to treat cancerous tumours with greater precision.”

For the past decade, Dr. Zheng’s research focus has been on finding novel ways to use heat, light and sound to advance multi-modality imaging and create unique, organic nanoparticle delivery platforms capable of transporting cancer therapeutics directly to tumours.

Interesting development, although I suspect there are many challenges yet to be met such as ensuring the microbubbles consistently arrive at their intended destination in sufficient mass to be effective both for imaging purposes and, later, as nanoparticles for drug delivery purposes.

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

In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging by Elizabeth Huynh, Ben Y. C. Leung, Brandon L. Helfield, Mojdeh Shakiba, Julie-Anne Gandier, Cheng S. Jin, Emma R. Master, Brian C. Wilson, David E. Goertz, & Gang Zheng. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.25 Published online 30 March 2015

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

This is one of those times where I’m including the funding agencies and the ‘About’ portions of the news release,

The research published today was funded by the Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship, the Emerging Team Grant on Regenerative Medicine and Nanomedicine co-funded by the CIHR and the Canadian Space Agency, the Natural Sciences and Engineering Research Council of Canada, the Ontario Institute for Cancer Research, the International Collaborative R&D Project of the Ministry of Knowledge Economy, South Korea, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research, the Canada Foundation for Innovation and The Princess Margaret Cancer Foundation.

About Princess Margaret Cancer Centre, University Health Network

The Princess Margaret Cancer Centre has achieved an international reputation as a global leader in the fight against cancer and delivering personalized cancer medicine. The Princess Margaret, one of the top five international cancer research centres, is a member of the University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. All are research hospitals affiliated with the University of Toronto. For more information, go to http://www.theprincessmargaret.ca or http://www.uhn.ca .

I was not expecting to see South Korea or Brazil mentioned in the funding. Generally, when multiple countries are funding research, their own research institutions are also involved. As for the Princess Margaret Cancer Centre being one of the top five such centres internationally, I wonder how these rankings are determined.

And the bacteria shall save us—nanobiobots

A March 24, 2015 University of Illinois at Chicago news release (also on EurekAlert) describes the NERD, a Nano-Electro-Robotic Device which employs bacteria and graphene quantum dots,

As nanotechnology makes possible a world of machines too tiny to see, researchers are finding ways to combine living organisms with nonliving machinery to solve a variety of problems.

Like other first-generation bio-robots, the new nanobot engineered at the University of Illinois at Chicago [UIC] is a far cry from Robocop. It’s a robotic germ.

UIC researchers created an electromechanical device–a humidity sensor–on a bacterial spore. They call it NERD, for Nano-Electro-Robotic Device. …

“We’ve taken a spore from a bacteria, and put graphene quantum dots on its surface–and then attached two electrodes on either side of the spore,” said Vikas Berry, UIC associate professor of chemical engineering and principal investigator on the study.

“Then we change the humidity around the spore,” he said.

When the humidity drops, the spore shrinks as water is pushed out. As it shrinks, the quantum dots come closer together, increasing their conductivity, as measured by the electrodes.

“We get a very clean response–a very sharp change the moment we change humidity,” Berry said. The response was 10 times faster, he said, than a sensor made with the most advanced man-made water-absorbing polymers.

There was also better sensitivity in extreme low-pressure, low-humidity situations.

“We can go all the way down to a vacuum and see a response,” said Berry, which is important in applications where humidity must be kept low, for example, to prevent corrosion or food spoilage. “It’s also important in space applications, where any change in humidity could signal a leak,” he said.

Currently available sensors increase in sensitivity as humidity rises, Berry said. NERD’s sensitivity is actually higher at low humidity.

“This is a fascinating device,” Berry said. “Here we have a biological entity. We’ve made the sensor on the surface of these spores, with the spore a very active complement to this device. The biological complement is actually working towards responding to stimuli and providing information.”

Interesting, yes? Here’s a link to and a citation for the research paper,

Graphene Quantum Dots Interfaced with Single Bacterial Spore for Bio-Electromechanical Devices: A Graphene Cytobot by T. S. Sreeprasad, Phong Nguyen, Ahmed Alshogeathri, Luke Hibbeler, Fabian Martinez, Nolan McNeil, & Vikas Berry. Scientific Reports 5, Article number: 9138 doi:10.1038/srep09138 Published 16 March 2015

This paper is open access.

Dexter Johnson provides more context for this research in a March 26, 2015 post on his Nanoclast blog (on the IEEE [institute of Electrical and Electronics Engineers]) where he notes,

Recently, James Tours’ group at Rice University, who were the first to develop GQCs [graphene quantum dots] in 2013, created an improved way to manufacture them that promised to open them up to a new range of applications in optics.

Dexter’s insights make for worthwhile reading.

What is a buckybomb?

I gather buckybombs have something to do with cancer treatments. From a March 18, 2015 news item on ScienceDaily,

In 1996, a trio of scientists won the Nobel Prize for Chemistry for their discovery of Buckminsterfullerene — soccer-ball-shaped spheres of 60 joined carbon atoms that exhibit special physical properties.

Now, 20 years later, scientists have figured out how to turn them into Buckybombs.

These nanoscale explosives show potential for use in fighting cancer, with the hope that they could one day target and eliminate cancer at the cellular level — triggering tiny explosions that kill cancer cells with minimal impact on surrounding tissue.

“Future applications would probably use other types of carbon structures — such as carbon nanotubes, but we started with Bucky-balls because they’re very stable, and a lot is known about them,” said Oleg V. Prezhdo, professor of chemistry at the USC [University of Southern California] Dornsife College of Letters, Arts and Sciences and corresponding author of a paper on the new explosives that was published in The Journal of Physical Chemistry on February 24 [2015].

A March 19, 2015 USC news release by Robert Perkins, which despite its publication date originated the news item, describes current cancer treatments with carbon nanotubes and this new technique with fullerenes,

Carbon nanotubes, close relatives of Bucky-balls, are used already to treat cancer. They can be accumulated in cancer cells and heated up by a laser, which penetrates through surrounding tissues without affecting them and directly targets carbon nanotubes. Modifying carbon nanotubes the same way as the Buckybombs will make the cancer treatment more efficient — reducing the amount of treatment needed, Prezhdo said.

To build the miniature explosives, Prezhdo and his colleagues attached 12 nitrous oxide molecules to a single Bucky-ball and then heated it. Within picoseconds, the Bucky-ball disintegrated — increasing temperature by thousands of degrees in a controlled explosion.

The source of the explosion’s power is the breaking of powerful carbon bonds, which snap apart to bond with oxygen from the nitrous oxide, resulting in the creation of carbon dioxide, Prezhdo said.

I’m glad this technique would make treatment more effective but I do pause at the thought of having exploding buckyballs in my body or, for that matter, anyone else’s.

The research was highlighted earlier this month in a March 5, 2015 article by Lisa Zynga for phys.org,

The buckybomb combines the unique properties of two classes of materials: carbon structures and energetic nanomaterials. Carbon materials such as C60 can be chemically modified fairly easily to change their properties. Meanwhile, NO2 groups are known to contribute to detonation and combustion processes because they are a major source of oxygen. So, the scientists wondered what would happen if NO2 groups were attached to C60 molecules: would the whole thing explode? And how?

The simulations answered these questions by revealing the explosion in step-by-step detail. Starting with an intact buckybomb (technically called dodecanitrofullerene, or C60(NO2)12), the researchers raised the simulated temperature to 1000 K (700 °C). Within a picosecond (10-12 second), the NO2 groups begin to isomerize, rearranging their atoms and forming new groups with some of the carbon atoms from the C60. As a few more picoseconds pass, the C60 structure loses some of its electrons, which interferes with the bonds that hold it together, and, in a flash, the large molecule disintegrates into many tiny pieces of diatomic carbon (C2). What’s left is a mixture of gases including CO2, NO2, and N2, as well as C2.

I encourage you to read Zynga’s article in whole as she provides more scientific detail and she notes that this discovery could have applications for the military and for industry.

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

Buckybomb: Reactive Molecular Dynamics Simulation by Vitaly V. Chaban, Eudes Eterno Fileti, and Oleg V. Prezhdo. J. Phys. Chem. Lett., 2015, 6 (5), pp 913–917 DOI: 10.1021/acs.jpclett.5b00120 Publication Date (Web): February 24, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.