Tag Archives: US

A nanoparticle for a medical imaging machine that doesn’t exist yet

Researchers at the University of Buffalo (New York state) have created a nanoparticle that can be detected by six imaging devices according to a Jan. 20, 2015 news item on ScienceDaily,

It’s technology so advanced that the machine capable of using it doesn’t yet exist.

Using two biocompatible parts, University at Buffalo researchers and their colleagues have designed a nanoparticle that can be detected by six medical imaging techniques:

• computed tomography (CT) scanning;

• positron emission tomography (PET) scanning;

• photoacoustic imaging;

• fluorescence imaging;

• upconversion imaging; and

• Cerenkov luminescence imaging.

The advantages are obvious should somebody, somewhere create a hexamodal (aka, multimodal, aka hypmodal) sensing device capable of exploiting the advantages of this nanoparticle as the researchers hope.

A Jan. 20, 2015 University of Buffalo news release (also on EurekAlert) by Charlotte Hsu, which originated the news item, describes the ideas underlying the research,

This kind of “hypermodal” imaging — if it came to fruition — would give doctors a much clearer picture of patients’ organs and tissues than a single method alone could provide. It could help medical professionals diagnose disease and identify the boundaries of tumors.

“This nanoparticle may open the door for new ‘hypermodal’ imaging systems that allow a lot of new information to be obtained using just one contrast agent,” says researcher Jonathan Lovell, PhD, UB assistant professor of biomedical engineering. “Once such systems are developed, a patient could theoretically go in for one scan with one machine instead of multiple scans with multiple machines.”

When Lovell and colleagues used the nanoparticles to examine the lymph nodes of mice, they found that CT and PET scans provided the deepest tissue penetration, while the photoacoustic imaging showed blood vessel details that the first two techniques missed.

Differences like these mean doctors can get a much clearer picture of what’s happening inside the body by merging the results of multiple modalities.

A machine capable of performing all six imaging techniques at once has not yet been invented, to Lovell’s knowledge, but he and his coauthors hope that discoveries like theirs will spur development of such technology.

The news release also offers a description of the nanoparticles,

The researchers designed the nanoparticles from two components: An “upconversion” core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core.

Each part has unique characteristics that make it ideal for certain types of imaging.

The core, initially designed for upconversion imaging, is made from sodium, ytterbium, fluorine, yttrium and thulium. The ytterbium is dense in electrons — a property that facilitates detection by CT scans.

The PoP wrapper has biophotonic qualities that make it a great match for fluorescence and photoacoustic imagining. The PoP layer also is adept at attracting copper, which is used in PET and Cerenkov luminescence imaging.

“Combining these two biocompatible components into a single nanoparticle could give tomorrow’s doctors a powerful, new tool for medical imaging,” says Prasad, also a SUNY Distinguished Professor of chemistry, physics, medicine and electrical engineering at UB. “More studies would have to be done to determine whether the nanoparticle is safe to use for such purposes, but it does not contain toxic metals such as cadmium that are known to pose potential risks and found in some other nanoparticles.”

“Another advantage of this core/shell imaging contrast agent is that it could enable biomedical imaging at multiple scales, from single-molecule to cell imaging, as well as from vascular and organ imaging to whole-body bioimaging,” Chen adds. “These broad, potential capabilities are due to a plurality of optical, photoacoustic and radionuclide imaging abilities that the agent possesses.”

Lovell says the next step in the research is to explore additional uses for the technology.

For example, it might be possible to attach a targeting molecule to the PoP surface that would enable cancer cells to take up the particles, something that photoacoustic and fluorescence imaging can detect due to the properties of the smart PoP coating. This would enable doctors to better see where tumors begin and end, Lovell says.

The researchers have provided two images,

This transmission electron microscopy image shows the nanoparticles, which consist of a core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core. Credit: Jonathan Lovell

This transmission electron microscopy image shows the nanoparticles, which consist of a core that glows blue when struck by near-infrared light, and an outer fabric of porphyrin-phospholipids (PoP) that wraps around the core.
Credit: Jonathan Lovell

University at Buffalo researchers and colleagues have designed a nanoparticle detectable by six medical imaging techniques. This illustration depicts the particles as they are struck by beams of energy and emit signals that can be detected by the six methods: CT and PET scanning, along with photoacoustic, fluorescence, upconversion and Cerenkov luminescence imaging. Credit: Jonathan Lovell

University at Buffalo researchers and colleagues have designed a nanoparticle detectable by six medical imaging techniques. This illustration depicts the particles as they are struck by beams of energy and emit signals that can be detected by the six methods: CT and PET scanning, along with photoacoustic, fluorescence, upconversion and Cerenkov luminescence imaging.
Credit: Jonathan Lovell

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

Hexamodal Imaging with Porphyrin-Phospholipid-Coated Upconversion Nanoparticles by James Rieffel, Feng Chen, Jeesu Kim, Guanying Chen, Wei Shao, Shuai Shao, Upendra Chitgupi, Reinier Hernandez, Stephen A. Graves, Robert J. Nickles, Paras N. Prasad, Chulhong Kim, Weibo Cai, and Jonathan F. Lovell. Advanced Materials DOI: 10.1002/adma.201404739 Article first published online: 14 JAN 2015

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

This article is behind a paywall.

The perfect keyboard: it self-cleans and self-powers and it can identify its owner(s)

There’s a pretty nifty piece of technology being described in a Jan. 21, 2015 news item on Nanowerk, which focuses on the security aspects first (Note: A link has been removed),

In a novel twist in cybersecurity, scientists have developed a self-cleaning, self-powered smart keyboard that can identify computer users by the way they type. The device, reported in the journal ACS Nano (“Personalized Keystroke Dynamics for Self-Powered Human–Machine Interfacing”), could help prevent unauthorized users from gaining direct access to computers.

A Jan. 21, 2015 American Chemical Society (ACS) news release (also on EurekAlert), which originated the news item, continues with the keyboard’s security features before briefly mentioning the keyboard’s self-powering and self-cleaning capabilities,

Zhong Lin Wang and colleagues note that password protection is one of the most common ways we control who can log onto our computers — and see the private information we entrust to them. But as many recent high-profile stories about hacking and fraud have demonstrated, passwords are themselves vulnerable to theft. So Wang’s team set out to find a more secure but still cost-effective and user-friendly approach to safeguarding what’s on our computers.

The researchers developed a smart keyboard that can sense typing patterns — including the pressure applied to keys and speed — that can accurately distinguish one individual user from another. So even if someone knows your password, he or she cannot access your computer because that person types in a different way than you would. It also can harness the energy generated from typing to either power itself or another small device. And the special surface coating repels dirt and grime. The scientists conclude that the keyboard could provide an additional layer of protection to boost the security of our computer systems.

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

Personalized Keystroke Dynamics for Self-Powered Human–Machine Interfacing by Jun Chen, Guang Zhu, Jin Yang, Qingshen Jing, Peng Bai, Weiqing Yang, Xuewei Qi, Yuanjie Su, and Zhong Lin Wang. ACS Nano, Article ASAP DOI: 10.1021/nn506832w Publication Date (Web): December 30, 2014

Copyright © 2014 American Chemical Society

This paper is behind a paywall. I did manage a peek at the paper and found that the keyboard is able to somehow harvest the mechanical energy of typing and turn it into electricity so it can self-power. Self-cleaning is made possible by a nanostructure surface modification. An idle thought and a final comment. First, I wonder what happens if you want to or have to share your keyboard? Second, a Jan. 21, 2015 article about the intelligent keyboard by Luke Dormehl for Fast Company notes that the researchers are from the US and China and names two of the institutions involved in this collaboration, Georgia Institute of Technology and the Beijing Institute of Nanoenergy and Nanosystems,.

ETA Jan. 23, 2015: There’s a Georgia Institute of Technology Jan. 21, 2015 news release on EurekAlert about the intelligent keyboard which offers more technical details such as these,

Conventional keyboards record when a keystroke makes a mechanical contact, indicating the press of a specific key. The intelligent keyboard records each letter touched, but also captures information about the amount of force applied to the key and the length of time between one keystroke and the next. Such typing style is unique to individuals, and so could provide a new biometric for securing computers from unauthorized use.

In addition to providing a small electrical current for registering the key presses, the new keyboard could also generate enough electricity to charge a small portable electronic device or power a transmitter to make the keyboard wireless.

An effect known as contact electrification generates current when the user’s fingertips touch a plastic material on which a layer of electrode material has been coated. Voltage is generated through the triboelectric and electrostatic induction effects. Using the triboelectric effect, a small charge can be produced whenever materials are brought into contact and then moved apart.

“Our skin is dielectric and we have electrostatic charges in our fingers,” Wang noted. “Anything we touch can become charged.”

Instead of individual mechanical keys as in traditional keyboards, Wang’s intelligent keyboard is made up of vertically-stacked transparent film materials. Researchers begin with a layer of polyethylene terephthalate between two layers of indium tin oxide (ITO) that form top and bottom electrodes.

Next, a layer of fluorinated ethylene propylene (FEP) is applied onto the ITO surface to serve as an electrification layer that generates triboelectric charges when touched by fingertips. FEP nanowire arrays are formed on the exposed FEP surface through reactive ion etching.

The keyboard’s operation is based on coupling between contact electrification and electrostatic induction, rather than the traditional mechanical switching. When a finger contacts the FEP, charge is transferred at the contact interface, injecting electrons from the skin into the material and creating a positive charge.

When the finger moves away, the negative charges on the FEP side induces positive charges on the top electrode, and equal amounts of negative charges on the bottom electrode. Consecutive keystrokes produce a periodic electrical field that drives reciprocating flows of electrons between the electrodes. Though eventually dissipating, the charges remain on the FEP surface for an extended period of time.

Wang believes the new smart keyboard will be competitive with existing keyboards, in both cost and durability. The new device is based on inexpensive materials that are widely used in the electronics industry.

Multi-walled carbon nanotubes and blood clotting

There’s been a lot of interest in using carbon nanotubes (CNTs) for biomedical applications such as drug delivery. New research from Trinity College Dublin (TCD) suggests that multi-walled carbon nanotubes (MWCNTs) may have some limitations when applied to biomedical uses. From a Jan. 20, 2014 news item on Nanowerk (Note: A link has been removed),

Scientists in the School of Pharmacy and Pharmaceutical Sciences in Trinity College Dublin, have made an important discovery about the safety issues of using carbon nanotubes as biomaterials which come into contact with blood. The significance of their findings is reflected in their paper being published as the feature story and front page cover of the international, peer-reviewed journal Nanomedicine (“Blood biocompatibility of surface-bound multi-walled carbon nanotubes”).

A Jan. 19, 2015 TCD press release, which originated the news item, offers a good description of the issues around blood clotting and the research problem (nonfunctionalized CNTs and blood compartibility) the scientists were addressing (Note: Links have been removed),

When blood comes into contact with foreign surfaces the blood’s platelets are activated which in turn leads to blood clots being formed. This can be catastrophic in clinical settings where extracorporeal circulation technologies are used such as during heart-lung bypass, in which the blood is circulated in PVC tubing outside the body. More than one million cardiothoracic surgeries are performed each year and while new circulation surfaces that prevent platelet activation are urgently needed, effective technologies have remained elusive.

One hope has been that carbon nanotubes, which are enormously important as potentially useful biomedical materials, might provide a solution to this challenge and this led the scientists from the School of Pharmacy and Pharmaceutical Sciences in collaboration with Trinity’s School of Chemistry and with colleagues from UCD and the University of Michigan in Ann Arbour to test the blood biocompatibility of carbon nanotubes. They found that the carbon nanotubes did actually stimulate blood platelet activation, subsequently leading to serious and devastating blood clotting. The findings have implications for the design of medical devices which contain nanoparticles and which are used in conjunction with flowing blood.

Speaking about their findings, Professor Marek Radomski, Chair of Pharmacology, Trinity and the paper’s senior author said: “Our results bear significance for the design of blood-facing medical devices, surface-functionalised with nanoparticles or containing surface-shedding nanoparticles. We feel that the risk/benefit ratio with particular attention to blood compatibility should be carefully evaluated during the development of such devices. Furthermore, it is clear that non-functionalised carbon nanotubes both soluble and surface-bound are not blood-compatible”.

The press release also quotes a TCD graduate,

Speaking about the significance of these findings for Nanomedicine research, the paper’s first author Dr Alan Gaffney, a Trinity PhD graduate who is now Assistant Professor of Anaesthesiology in Columbia University Medical Centre, New York said: “When new and exciting technologies with enormous potential benefits for medicine are being studied, there is often a bias towards the publication of positive findings. [emphasis mine] The ultimate successful and safe application of nanotechnology in medicine requires a complete understanding of the negative as well as positive effects so that un-intended side effects can be prevented. Our study is an important contribution to the field of nanomedicine and nanotoxicology research and will help to ensure that nanomaterials that come in contact with blood are thoroughly tested for their interaction with blood platelets before they are used in patients.”

Point well taken Dr. Gaffney. Too often there’s an almost euphoric quality to the nanomedicine discussion where nanoscale treatments are described as if they are perfectly benign in advance of any real testing. For example, I wrote about surgical nanobots being used in a human clinical trial in a Jan. 7, 2015 post which features a video of the researcher ‘selling’ his idea. The enthusiasm is laudable and necessary (researchers work for years trying to develop new treatments) but as Gaffney notes there needs to be some counter-ballast and recognition of the ‘positive bias’ issue.

Getting back to the TCD research, here’s a link to and a citation for the paper (or counter-ballast),

Blood biocompatibility of surface-bound multi-walled carbon nanotubes by Alan M. Gaffney, MD, PhD, Maria J. Santos-Martinez, MD, Amro Satti, Terry C. Major, Kieran J. Wynne, Yurii K. Gun’ko, PhD, Gail M. Annich, Giuliano Elia, Marek W. Radomski, MD. January 2015 Volume 11, Issue 1, Pages 39–46 DOI: http://dx.doi.org/10.1016/j.nano.2014.07.005 Published Online: July 26, 2014

This paper is open access.

Microplasm-generated gold nanoparticles and the heart

Scientists are hoping they’ve found a better way to detect early signs of a heart attack according to a Jan. 15, 2015 news item on Nanotechnology Now,

NYU [New York University] Polytechnic School of Engineering professors have been collaborating with researchers from Peking University on a new test strip that is demonstrating great potential for the early detection of certain heart attacks.

Kurt H. Becker, a professor in the Department of Applied Physics and the Department of Mechanical and Aerospace Engineering, and WeiDong Zhu, a research associate professor in the Department of Mechanical and Aerospace Engineering, are helping develop a new colloidal gold test strip for cardiac troponin I (cTn-I) detection. The new strip uses microplasma-generated gold nanoparticles (AuNPs) and shows much higher detection sensitivity than conventional test strips. The new cTn-I test is based on the specific immune-chemical reactions between antigen and antibody on immunochromatographic test strips using AuNPs.

A Jan. 14, 2015 NYU Polytechnic School of Engineering news release (also on EurekAlert but dated Jan. 15, 2015), which originated the news item, explains what makes these new test strips more sensitive (hint: microplasma-generated gold nanoparticles),

Compared to AuNPs produced by traditional chemical methods, the surfaces of the gold nanoparticles generated by the microplasma-induced liquid chemical process attract more antibodies, which results in significantly higher detection sensitivity.

cTn-I is a specific marker for myocardial infarction. The cTn-I level in patients experiencing cardiac infarction is several thousand times higher than in healthy people. The early detection of cTn-I is therefore a key factor of heart attack diagnosis and therapy.

The use of microplasmas to generate AuNP is yet another application of the microplasma technology developed by Becker and Zhu.  Microplasmas have been used successfully in dental applications (improved bonding, tooth whitening, root canal disinfection), biological decontamination (inactivation of microorganisms and biofilms), and disinfection and preservation of fresh fruits and vegetables.

The microplasma-assisted synthesis of AuNPs has great potential for other biomedical and therapeutic applications such as tumor detection, cancer imaging, drug delivery, and treatment of degenerative diseases such as Alzheimer’s.

The routine use of gold nanoparticles in therapy and disease detection in patients is still years away: longer for therapeutic applications and shorter for biosensors. The biggest hurdle to overcome is the fact that the synthesis of monodisperse, size-controlled gold nanoparticles, even using microplasmas, is still a costly, time-consuming, and labor-intensive process, which limits their use currently to small-scale clinical studies, Becker explained.

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

Microplasma-Assisted Synthesis of Colloidal Gold Nanoparticles and Their Use in the Detection of Cardiac Troponin I (cTn-I) by Ruixue Wang, Shasha Zuo, Dong Wu, Jue Zhang, Weidong Zhu, Kurt H. Becker, and Jing Fang. Plasma Processes and Polymers DOI: 10.1002/ppap.201400127 Article first published online: 11 DEC 2014

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This article is behind a paywall.

For anyone curious about the more common chemical methods of producing gold nanoparticles, there’s this video produced in Australia by TechNyou Education. There’s a specific technique described which I believe is one of the most commonly used and I think this can be generalized to other gold nanoparticle chemical production processes,

One more thing, this video runs over my 5 min. policy limit for videos. To do this, I battled my inclination to include something that I think is useful for understanding more about nanoparticles and my desire to make sure that my blog doesn’t get too bloated.

Of airborne nanomaterials, bacterial microbiomes, viral microbiomes, and paper sensors

There’s a Jan. 14, 2015 news item on Nanowerk from the Virginia Polytechnic Institute (Virginia Tech) which is largely a personal profile featuring some basic information (useful for those new to the topic) about airborne nanoparticles (Note: A link has been removed),

The Harvard educated undergraduate [Linsey Marr,  professor of civil and environmental engineering, Virginia Tech] who obtained her Ph.D. from University of California at Berkeley and trained as a postdoctoral researcher with a Nobel laureate of chemistry at MIT is now among a handful of researchers in the world who are addressing concerns about engineered nanomaterials in the atmosphere.

Marr is part of the National Science Foundation’s Center for the Environmental Implications of Nanotechnology and her research group has characterized airborne nanoparticles at every point of their life cycle. This cycle includes production at a commercial manufacturing facility, use by consumers in the home, and disposal via incineration.

A Jan. 14, 2015 Virginia Tech news release, which originated the news item, quotes Marr on the current thinking about airborne nanoparticles,

“Results have shown that engineered nanomaterials released into the air are often aggregated with other particulate matter, such as combustion soot or ingredients in consumer spray products, and that the size of such aggregates may range from smaller than 10 nanometers to larger than 10 microns,” Marr revealed. She was referring to studies completed by research group members Marina Quadros Vance of Florianopolis, Brazil, a research scientist with the Virginia Tech Institute of Critical Technology and Applied Science, and Eric Vejerano, of Ligao, Philippines, a post-doctoral associate in civil and environmental engineering.

Size matters if these aggregates are inhaled.

Another concern is the reaction of a nanomaterial such as a fullerene with ozone at environmentally relevant concentration levels. Marr’s graduate student, Andrea Tiwari, of Mankato, Minnesota, said the resulting changes in fullerene could lead to enhanced toxicity.

The story then segues into airborne pathogens and viruses eventually honing in on virus microbiomes and bacterial microbiomes (from the news release),

Marr is a former Ironman triathlete who obviously has strong interests in what she is breathing into her own body. So it would be natural for her to expand her study of engineered nanoparticles traveling in the atmosphere to focus on airborne pathogens.

She did so by starting to consider the influenza virus as an airborne pollutant. She applied the same concepts and tools used for studying environmental contaminants and ambient aerosols to the examination of the virus.

She looked at viruses as “essentially self-assembled nanoparticles that are capable of self-replication.”

Her research team became the first to measure influenza virus concentrations in ambient air in a children’s day care center and on airplanes. When they conducted their studies, the Virginia Tech researchers collected samples from a waiting room of a health care center, two toddlers’ rooms and one babies’ area of a childcare center, as well as three cross-country flights between Roanoke, Virginia., and San Francisco. They collected 16 samples between Dec. 10, 2009 and Apr. 22, 2010.

“Half of the samples were confirmed to contain aerosolized influenza A viruses,” Marr said. The childcare samples were the most infected at 75 percent. Next, airplane samples reached 67 percent contamination, and health center numbers came in at 33 percent.

This study serves as a foundation for new work started about a year ago in her lab.

Marr collaborated with Aaron J. Prussin II, of Blacksburg, Virginia, and they successfully secured for him a postdoctoral fellowship from the Alfred P. Sloan Foundation to characterize the bacterial and viral microbiome — the ecological community of microorganisms — of the air in a daycare center.

They are now attempting to determine seasonal changes of both the viral microbiome and the bacterial microbiome in a daycare setting, and examine how changes in the microbiome are related to naturally occurring changes in the indoor environment.

“Little is known about the viral component of the microbiome and it is important because viruses are approximately 10 times more abundant than bacteria, and they help shape the bacterial community. Research suggests that viruses do have both beneficial and harmful interactions with bacteria,” Prussin said.

With Prussin and Marr working together they hope to verify their hypothesis that daycare centers harbor unique, dynamic microbiomes with plentiful bacteria and viruses. They are also looking at what seasonal changes might bring to a daycare setting.

They pointed to the effect of seasonal changes because in previous work, Marr, her former graduate student Wan Yang, of Shantou, China, and Elankumaran Subbiah, a virologist in the biomedical sciences and pathobiology department of the Virginia-Maryland College of Veterinary Medicine, measured the influenza A virus survival rate at various levels of humidity.

Their 2012 study presented for the first time the relationship between the influenza A virus viability in human mucus and humidity over a large range of relative humidities, from 17 percent to 100 percent. They found the viability of the virus was highest when the relative humidity was either close to 100 percent or below 50 percent. The results in human mucus may help explain influenza’s seasonality in different regions.

According to the news release Marr and her colleagues have developed a fast and cheap technology for detection of airborne pathogens (Note: A link has been removed),

With the urgent need to understand the dynamics of airborne pathogens, especially as one considers the threats of bioterrorism, pandemic influenza, and other emerging infectious diseases, Marr said “a breakthrough technology is required to enable rapid, low-cost detection of pathogens in air.”

Along with Subbiah and Peter Vikesland,  professor of civil and environmental engineering, they want to develop readily deployable, inexpensive, paper-based sensors for airborne pathogen detection.

In 2013 they received funding of almost $250,000 from Virginia Tech’s Institute for Critical Technology and Applied Science, a supporter of the clustering of research groups, to support their idea of creating paper-based sensors based on their various successes to date.

Marr explained the sensors “would use a sandwich approach. The bottom layer is paper containing specialized DNA that will immobilize the virus. The middle layer is the virus, which sticks to the specialized DNA on the bottom layer. The top layer is additional specialized DNA that sticks to the virus. This DNA is attached to gold nanoparticles that are easily detectable using a technique known as Raman microscopy.”

They key to their approach is that it combines high-tech with low-tech in the hopes of keeping the assay costs low. Their sampling method will use a bicycle pump, and low cost paper substrates. They hope that they will be able to incorporate smart-phone based signal transduction for the detection. Using this approach, they believe “even remote corners of the world” would be able to use the technique.

Vikesland previously received funding from the Gates Foundation to detect the polio virus via paper-based diagnostics. Polio is still found in countries on the continents of Asia and Africa.

I have previously mentioned Linsey Marr in an Oct. 18, 2013 post about the revival of the Nanotechnology Consumer Products Inventory (originally developed by the Project for Emerging Nanotechnologies) by academics at Virginia Tech and first mentioned CEINT in an Aug. 15, 2011 post about a special project featuring a mesocosm at Duke University (North Carolina).

A newish Tekmira results from a merger with OnCore Biopharma

A Jan. 12, 2015 news item on Azonano announces a new business entity, a combined Tekmira Pharmaceuticals (located in North Vancouver, Canada) and OnCore Biopharma (located in Pennsylvania, US),

Tekmira Pharmaceuticals Corporation, a leading developer of RNA interference (RNAi) therapeutics, and OnCore Biopharma, Inc., a biopharmaceutical company dedicated to discovering, developing and commercializing an all-oral cure for patients suffering from chronic hepatitis B virus (HBV) infection, announced today that they have agreed to merge to create a new leading global HBV company focused on developing a curative regimen for hepatitis B patients by combining multiple therapeutic approaches.

A Jan. 11, 2015 Tekmira news release, which originated the news item, provides details including how this merger will affect the work on the Tekmira ebola treatment,

This transaction is expected to bring together the companies’ broad expertise in antiviral drug development, Tekmira’s Phase 1-ready HBV RNAi therapeutic and OnCore’s multiple HBV programs, to build a robust portfolio of compounds aimed at eradicating HBV. The combined company’s most advanced products are expected to be TKM-HBV, an RNAi therapeutic designed to eliminate HBV surface antigen (HBsAg) expression, a key component of host immune suppression, which is on track to begin human clinical trials in the first quarter of 2015; and OCB-030, a second-generation cyclophilin inhibitor focused on the suppression of viral replication, as well as stimulation and reactivation of the body’s immune response, which is anticipated to enter human clinical trials in the second half of 2015. The combined company anticipates progressing additional programs toward the clinic to achieve the goal of expeditiously evaluating combination regimens.

The combined pipeline is expected to target the three pillars necessary to develop a curative regimen for HBV, including assets focused on suppressing HBV replication, reactivating and stimulating the host immune response directed at HBV and eliminating covalently closed circular DNA (cccDNA). The parties believe that, together, these three pillars are the foundation for achieving a curative regimen.

Dr. Mark J. Murray, Chief Executive Officer of Tekmira, said, “We believe that the merger between Tekmira and OnCore has the potential to transform the HBV treatment landscape by bringing together the technologies and science needed to eradicate the virus and develop a cure for this debilitating and deadly disease. Our new company has the potential to advance multiple, highly active, complementary agents into the clinic in rapid succession, and create an HBV therapeutics powerhouse, thereby potentially offering significant benefits to the global medical community working to improve the lives of HBV patients. Importantly, we also believe this transaction has the potential to create significant value for our shareholders.”

Patrick Higgins, Chief Executive Officer of OnCore, said, “Tekmira and OnCore share a vision that effective combination regimens will ultimately cure HBV, a goal now being realized for hepatitis C virus. This merger is expected to bring together the promise of TKM-HBV with our existing HBV portfolio and accelerate our timeline for combination clinical trials. It is expected to deliver both near-term catalysts and long-term value creation. We believe that the ability to rapidly and sequentially combine novel HBV therapeutics is extremely valuable. We intend to utilize our collective expertise in liver disease and a focused development program, as we did at Pharmasset, to expeditiously and efficiently meet our shared goals.”

An Industry-Leading, Multi-Functional HBV Portfolio

Through the combined portfolio, OnCore and Tekmira intend to advance a robust pipeline of assets that uniquely targets the three pillars for delivering a curative regimen for HBV, including suppressing HBV replication, reactivating and stimulating the host immune response directed at HBV and eliminating cccDNA, the stable source of HBV viral genomic material. Post-closing, the combined company’s HBV portfolio is expected to include  product assets, which can be viewed in a chart by clicking on the following  link: http://media.globenewswire.com/cache/14025/file/31117.pdf

“We intend to take a focused, iterative approach to identifying the most effective combination regimens, while applying what we learn at each stage to optimize future compounds and combinations,” said Dr. Michael Sofia, the combined company’s Chief Scientific Officer and an inventor of sofosbuvir (Sovaldi) for the treatment of hepatitis C. “We believe that the ability to combine multiple unique programs housed in the same company is a significant competitive advantage, and should provide considerable efficiency in terms of speed and ease of decision-making. Combining the OnCore and Tekmira HBV portfolios underpins our vision to accelerate the delivery of a curative HBV regimen.”

Non-HBV Programs Continuing to Move Forward

Tekmira is a global leader in the RNAi field, and has created a diverse pipeline of products in development to treat serious human diseases, such as cancer and viral infections, including Ebola. The company has also licensed its leading lipid nanoparticle (LNP) delivery technology to partners around the world.

The management teams and Boards of Directors of Tekmira and OnCore believe that there is significant value in Tekmira’s non-HBV assets and collaborations. TKM-PLK1 is currently in Phase 2 in multiple indications and TKM-Ebola is expected to enter Phase 2 in West Africa in early 2015. Tekmira also maintains an active RNAi research and development effort. The combined management team and Board of Directors plans to continue to move forward with these programs with the goal of maximizing their value.

The news release goes on to describe the deal,

Under the terms of the agreement, the transaction will be carried out by way of a merger pursuant to which OnCore will merge with a wholly-owned subsidiary of Tekmira and thereby become a wholly-owned subsidiary of Tekmira. Upon closing of the transaction the stockholders of OnCore will hold approximately fifty percent (50%) of the total number of outstanding shares of capital stock of Tekmira, calculated on a fully-diluted and as-converted basis using the treasury stock method. The terms and conditions of the transaction are more fully set forth in the Merger Agreement. The implied market value of the combined company, based on the closing price of Tekmira common shares on the NASDAQ Global Market on January 9, 2015, is approximately USD$750 million.

The merger is subject to approval of a majority of the shareholders of Tekmira present, in person or by proxy, at a special meeting of Tekmira shareholders. Completion of the transaction is also subject to customary closing conditions, including regulatory approvals.  The transaction is expected to close in the first half of 2015, shortly after completion of the Securities and Exchange Commission (SEC) review process and receipt of Tekmira shareholder approval. The Tekmira Board of Directors unanimously approved and recommends that Tekmira shareholders vote FOR the proposed transaction at a special meeting of shareholders.

Details regarding these and other terms of the transaction are set out in the Merger Agreement, which will be filed by Tekmira on the SEC website at www.sec.gov and on the Canadian securities administrator’s website at www.sedar.com.

The combined company plans to retain top executives and board members from Tekmira and OnCore. The new company’s management team will include Mark J. Murray, PhD, Chief Executive Officer; Patrick T. Higgins, President and Chief Operating Officer; Bruce Cousins, Chief Financial Officer; Michael J. Sofia, PhD, Chief Scientific Officer; Mark Kowalski, MD, PhD, Chief Medical Officer; Bryce Roberts, Chief Legal Officer; Michael J. McElhaugh, Chief Business Officer; and Michael J. Abrams, PhD, Chief Discovery Officer. William T. Symonds, PharmD, who led the clinical development of sofosbuvir for the treatment of HCV infection at Pharmasset and later Gilead Sciences, Inc., will be Chief Development Officer and lead the clinical development of the portfolio.

Vivek Ramaswamy will serve as Chairman of the combined company; Dr. Daniel Kisner MD will serve as its Vice-Chairman. The combined company will be headquartered in Vancouver, BC.

I don’t understand how a company, OnCore, which is becoming a subsidiary qualifies as an equal partner in a merger but I gather this is business speak. In any event, the truly curious can find the webcast for a conference call about the deal held on Jan. 12, 2015 at 5 am PT (8 am ET)  along with an accompanying presentation here. The webcast will be available only from January 12, 2015 at 9:00 am PT  / 12 noon ET to January 17, 2015 at 9:00 am PT  / 12 noon ET and, for access, you must register on the site.

I have written previously about Tekmira, in a Nov. 19, 2014 post regarding another of its business deals and in a Sept. 23, 2014 post about its ebola treatment.

Engineering a small intestine

Researchers at the Children’s Hospital Los Angeles (CHLA) have successfully engineered small intestines that appear to be functional when transplanted into mice according to a Jan. 8, 2015 news item on ScienceDaily,

A new study by researchers at Children’s Hospital Los Angeles has shown that tissue-engineered small intestine grown from human cells replicates key aspects of a functioning human intestine. The tissue-engineered small intestine they developed contains important elements of the mucosal lining and support structures, including the ability to absorb sugars, and even tiny or ultra-structural components like cellular connections.

A Jan. 8, 2015 Children’s Hospital Los Angeles news release (also on EurekAlert), which originated the news item, describes the problems the researchers were addressing,

Tissue-engineered small intestine (TESI) grows from stem cells contained in the intestine and offers a promising treatment for short bowel syndrome (SBS), a major cause of intestinal failure, particularly in premature babies and newborns with congenital intestinal anomalies.  TESI may one day offer a therapeutic alternative to the current standard treatment, which is intestinal transplantation, and could potentially solve its largest challenges – donor shortage and the need for lifelong immunosuppression.

Grikscheit [Tracy C. Grikscheit, MD, a principal investigator in The Saban Research Institute of CHLA and its Developmental Biology and Regenerative Medicine program]  aims to help her most vulnerable young patients, including babies who are born prematurely and develop a devastating disease called necrotizing enterocolitis (NEC), where life-threatening intestinal damage requires removal of large portions of the small intestine. Without enough intestinal length, the babies are dependent on intravenous feeding, which is costly and may cause liver damage.  NEC and other contributors to intestinal failure occur in 24.5 out of 100,000 live births, and the incidence of SBS is increasing.  Nearly a third of patients die within five years.

The news release goes on to describe precursor work from 2011 before describing the latest research,

CHLA scientists had previously shown that TESI could be generated from human small intestine donor tissue implanted into immunocompromised mice. However, in those initial studies – published in July 2011 in the biomedical journal Tissue Engineering, Part A – only basic components of the intestine were identified. For clinical relevance, it remained necessary to more fully investigate intact components of function such as the ability to form a healthy barrier while still absorbing nutrition or specific mechanisms of electrolyte exchange.

The new study determined that mouse TESI is highly similar to the TESI derived from human cells, and that both contain important building blocks such as the stem and progenitor cells that will continue to regenerate the intestine as a living tissue replacement. And these cells are found within the engineered tissue in specific locations and in close proximity to other specialized cells that are known to be necessary in healthy human intestine for a fully functioning organ.

“We have shown that we can grow tissue-engineered small intestine that is more complex than other stem cell or progenitor cell models that are currently used to study intestinal regeneration and disease, and proven it to be fully functional as it develops from human cells,” said Grikscheit. “Demonstrating the functional capacity of this tissue-engineered intestine is a necessary milestone on our path toward one day helping patients with intestinal failure.”

If I read this rightly, the researchers engineered more complex intestinal tissues, than those in the 2011 study, in two separate processes where they grew mouse and human small intestinal tissue and successfully implanted both types of tissue into mice. The results showed that these more complex tissue-engineered small intestines (TESIs), human or mouse, resembled each other functionally within the mice tested.

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

Human and Mouse Tissue-Engineered Small Intestine Both Demonstrate Digestive And Absorptive Function by Christa Nicole Grant, Garcia Mojica Salvador, Frederic G Sala, Jeffrey Ryan Hill, Daniel E Levin, Allison L Speer, Erik R Barthel, Hiroyuki Shimada, Nicholas C. Zachos, and Tracy C. Grikscheit. American Journal of Physiology – Gastrointestinal and Liver Physiology Published 8 January 2015Vol. no. , DOI: 10.1152/ajpgi.00111.2014

This paper is behind a paywall.

A new approach to heating: warm the clothing not the room

A Jan. 7, 2015 news item on ScienceDaily describes a new type of textile which could change the way we use heat (energy),

To stay warm when temperatures drop outside, we heat our indoor spaces — even when no one is in them. But scientists have now developed a novel nanowire coating for clothes that can both generate heat and trap the heat from our bodies better than regular clothes. They report on their technology, which could help us reduce our reliance on conventional energy sources, in the ACS journal Nano Letters.

A Jan. 7, 2015 American Chemical Society (ACS) news release (also on EurekAlert), which originated the news item, provides more information about energy consumption and the researchers’ proposed solution,

Yi Cui [Stanford University] and colleagues note that nearly half of global energy consumption goes toward heating buildings and homes. But this comfort comes with a considerable environmental cost – it’s responsible for up to a third of the world’s total greenhouse gas emissions. Scientists and policymakers have tried to reduce the impact of indoor heating by improving insulation and construction materials to keep fuel-generated warmth inside. Cui’s team wanted to take a different approach and focus on people rather than spaces.

The researchers developed lightweight, breathable mesh materials that are flexible enough to coat normal clothes. When compared to regular clothing material, the special nanowire cloth trapped body heat far more effectively. Because the coatings are made out of conductive materials, they can also be actively warmed with an electricity source to further crank up the heat. The researchers calculated that their thermal textiles could save about 1,000 kilowatt hours per person every year — that’s about how much electricity an average U.S. home consumes in one month.

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

Personal Thermal Management by Metallic Nanowire-Coated Textile by Po-Chun Hsu, Xiaoge Liu, Chong Liu, Xing Xie, Hye Ryoung Lee, Alex J. Welch, Tom Zhao, and Yi Cui. Nano Lett., Article ASAP DOI: 10.1021/nl5036572 Publication Date (Web): November 30, 2014
Copyright © 2014 American Chemical Society

This paper is behind a paywall.

Gelatin nanoparticles for drug delivery after a stroke

A Dec. 24, 2014 news item on phys.org describes a treatment that could mitigate the effects of a stroke by extending the window of opportunity for recuperative treatments (Note: Links have been removed),

Stroke victims could have more time to seek treatment that could reduce harmful effects on the brain, thanks to tiny blobs of gelatin that could deliver the medication to the brain noninvasively.

University of Illinois researchers and colleagues in South Korea, led by U. of I. electrical and computer engineering senior research scientist Hyungsoo Choi and professor Kyekyoon “Kevin” Kim, published details about the gelatin nanoparticles in the journal Drug Delivery and Translational Research.

A Dec. 23, 2014 University of Illinois at Urbana-Champaign news release, which originated the news item, explains how the gelatin nanoparticles are directed to the injury site (Note: links have been removed),

The researchers found that gelatin nanoparticles could be laced with medications for delivery to the brain, and that they could extend the treatment window for when a drug could be effective. Gelatin is biocompatible, biodegradable, and classified as “Generally Recognized as Safe” by the Food and Drug Administration. Once administered, the gelatin nanoparticles target damaged brain tissue thanks to an abundance of gelatin-munching enzymes produced in injured regions.

The tiny gelatin particles have a huge benefit: They can be administered nasally, a noninvasive and direct route to the brain. This allows the drug to bypass the blood-brain barrier, a biological fence that prevents the vast majority of drugs from entering the brain through the bloodstream.

“Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of most neurological disorders,” said Choi.  “However, if drug substances can be transferred along the olfactory nerve cells, they can bypass the blood-brain barrier and enter the brain directly.”

To test gelatin nanoparticles as a drug-delivery system, the researchers used the drug osteopontin (OPN), which in rats can help to reduce inflammation and prevent brain cell death if administered immediately after a stroke.

“It is crucial to treat ischemic strokes within three hours to improve the chances of recovery. However, a significant number of stroke victims don’t get to the hospital in time for the treatment,” Kim said.

By lacing gelatin nanoparticles with OPN, the researchers found that they could extend the treatment window in rats, so much so that treating a rat with nanoparticles six hours after a stroke showed the same efficacy rate as giving them OPN alone after one hour – 70 percent recovery of dead volume in the brain.

The researchers hope the gelatin nanoparticles, administered through the nasal cavity, can help deliver other drugs to more effectively treat a variety of brain injuries and neurological diseases.

“Gelatin nanoparticles are a delivery vehicle that could be used to deliver many therapeutics to the brain,” Choi said. “They will be most effective in delivering drugs that cannot cross the blood-brain barrier. In addition, they can be used for drugs of high toxicity or a short half-life.“

I expect the next steps will include some human clinical trials. In the meantime for those who are interested, here’s a link to and a citation for the paper,

Gelatin nanoparticles enhance the neuroprotective effects of intranasally administered osteopontin in rat ischemic stroke model by Elizabeth Joachim, Il-Doo Kim, Yinchuan Jin, Kyekyoon (Kevin) Kim, Ja-Kyeong Lee, and Hyungsoo Choi. Drug Delivery and Translational Research Volume 4, Issue 5-6 , pp 395-399 DOI 10.1007/s13346-014-0208-9 Published online Nov. 8, 2014

This paper is behind a paywall.

Quantum dots cycling through the food chain

Rice University (Texas, US) researchers have published a study which follows quantum dot nanoparticles as they enter the water supply and are taken up by plant roots and leaves and eaten by caterpillars. From a Dec. 16, 2014 news item on ScienceDaily,

In one of the most comprehensive laboratory studies of its kind, Rice University scientists traced the uptake and accumulation of quantum dot nanoparticles from water to plant roots, plant leaves and leaf-eating caterpillars.

The study, one of the first to examine how nanoparticles move through human-relevant food chains, found that nanoparticle accumulation in both plants and animals varied significantly depending upon the type of surface coating applied to the particles. The research is available online in the American Chemical Society’s journal Environmental Science & Technology.

A Dec. 16, 2014 Rice University news release (also on EurekAlert), which originated the news item, provides insight into some of the issues being addressed with this research (Note: Links have been removed),

“With industrial use of nanoparticles on the rise, there are increasing questions about how they move through the environment and whether they may accumulate in high levels in plants and animals that people eat,” said study co-author Janet Braam, professor and chair of the Department of BioSciences at Rice.

Braam and colleagues studied the uptake of fluorescent quantum dots by Arabidopsis thaliana, an oft-studied plant species that is a relative of mustard, broccoli and kale. In particular, the team looked at how various surface coatings affected how quantum dots moved from roots to leaves as well as how the particles accumulated in leaves. The team also studied how quantum dots behaved when caterpillars called cabbage loopers (Trichoplusia ni) fed upon plant leaves containing quantum dots.

“The impact of nanoparticle uptake on plants themselves and on the herbivores that feed upon them is an open question,” said study first author Yeonjong Koo, a postdoctoral research associate in Braam’s lab. “Very little work has been done in this area, especially in terrestrial plants, which are the cornerstone of human food webs.”

Some toxins, like mercury and DDT, tend to accumulate in higher concentrations as they move up the food chain from plants to animals. It is unknown whether nanoparticles may also be subject to this process, known as biomagnification.

While there are hundreds of types of nanoparticles in use, Koo chose to study quantum dots, submicroscopic bits of semiconductors that glow brightly under ultraviolet light. The fluorescent particles — which contained cadmium, selenium, zinc and sulfur — could easily be measured and imaged in the tests. In addition, the team treated the surface of the quantum dots with three different polymer coatings — one positively charged, one negatively charged and one neutral.

“In industrial applications, nanoparticles are often coated with a polymer to increase solubility, improve stability, enhance properties and for other reasons,” said study co-author Pedro Alvarez, professor and chair of Rice’s Department of Civil and Environmental Engineering. “We expect surface coatings to play a significant role in whether and how nanomaterials may accumulate in food webs.”

Previous lab studies had suggested that the neutral coatings might cause the nanoparticles to aggregate and form clumps that were so large that they would not readily move from a plant’s roots to its leaves. The experiments bore this out. Of the three particle types, only those with charged coatings moved readily through the plants, and only the negatively charged particles avoided clumping altogether. The study also found that the type of coating impacted the plants’ ability to biodegrade, or break down, the quantum dots.

Koo and colleagues found caterpillars that fed on plants containing quantum dots gained less weight and grew more slowly than caterpillars that fed on untainted leaves. By examining the caterpillar’s excrement, the scientists were also able to estimate whether cadmium, selenium and intact quantum dots might be accumulating in the animals. Again, the coating played an important role.

“Our tests were not specifically designed to measure bioaccumulation in caterpillars, but the data we collected suggest that particles with positively charged coatings may accumulate in cells and pose a risk of bioaccumulation,” Koo said. “Based on our findings, more tests should be conducted to determine the extent of this risk under a broader set of ecological conditions.”

The researchers have a couple of images illustrating their work,

The buildup of fluorescent quantum dots in the leaves of Arabidopsis plants is apparent in this photograph of the plants under ultraviolet light. Credit: Y. Koo/Rice University

The buildup of fluorescent quantum dots in the leaves of Arabidopsis plants is apparent in this photograph of the plants under ultraviolet light. Credit: Y. Koo/Rice University

And, there’s a caterpillar,

Cabbage looper

Cabbage looper

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

Fluorescence Reports Intact Quantum Dot Uptake into Roots and Translocation to Leaves of Arabidopsis thaliana and Subsequent Ingestion by Insect Herbivores by Yeonjong Koo, Jing Wang, Qingbo Zhang, Huiguang Zhu, E. Wassim Chehab, Vicki L. Colvin, Pedro J. J. Alvarez, and Janet Braam. Environ. Sci. Technol., Just Accepted Manuscript DOI: 10.1021/es5050562 Publication Date (Web): December 1, 2014

Copyright © 2014 American Chemical Society

This paper is open access but you must be registered on the website.

One final thought about the research, it did take place in a laboratory environment and there doesn’t seem to have been any soil involved so the uptake can not be directly compared (as I understand matters) to the uptake characteristics where plant cultivation requires soil. This seems to have been a study involving hydroponic framing practices.