(NanoRealm) - For the first time, scientists have succeeded in growing empty particles derived from a plant virus and have made them carry useful chemicals.

The external surface of these nano containers could be decorated with molecules that guide them to where they are needed in the body, before the chemical load is discharged to exert its effect on diseased cells. The containers are particles of the Cowpea mosaic virus, which is ideally suited for designing biomaterial at the nanoscale.

"This is a shot in the arm for all Cowpea mosaic virus technology," says Professor George Lomonossoff of the John Innes Centre, one of the authors on a paper to be published in the specialised nanotechnology scientific journal, Small.
Scientists have previously tried to empty virus particles of their genetic material using irradiation or chemical treatment. Though successful in rendering the particles non-infectious, these methods have not fully emptied the particles.

Scientists at the John Innes Centre, funded by the BBSRC and the John Innes Foundation, discovered they could assemble empty particles from precursors in plants and then extract them to insert chemicals of interest. Scientists at JIC and elsewhere had also previously managed to decorate the surface of virus particles with useful molecules.

"But now we can load them too, creating fancy chemical containers," says lead author Dr Dave Evans.

"This brings a huge change to the whole technology and opens up new areas of research," says Prof Lomonossoff. "We don't really know all the potential applications yet because such particles have not been available before. There is no history of them."
One application could be in cancer treatment. Integrins are molecules that appear on cancer cells. The virus particles could be coated externally with peptides that bind to integrins. This would mean the particles seek out cancer cells to the exclusion of healthy cells. Once bound to the cancer cell, the virus particle would release an anti-cancer agent that has been carried as an internal cargo.

Some current drugs damage healthy cells as well as the cancer, leading to hair loss and other side effects. This technology could deliver the drug in a more targeted way.
"The potential for developing Cowpea mosaic virus as a targeted delivery agent of therapeutics is now a reality," says Dr Evans.

The empty viral particles, their use, and the processes by which they are made, are the subject of a new patent filing. Management of the patent and commercialisation of the technology is being handled by PBL.

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More information: "Cowpea Mosaic Virus Unmodified Empty Virus-Like Particles Can Be Loaded with Metal and Metal Oxide." DOI:10.1002/smll.200902135

Provided by Norwich BioScience Institutes

(NanoRealm) - Huixin He, associate professor, nanoscale chemistry at Rutgers University, Newark, and Tamara Minko, professor at the Rutgers Ernest Mario School of Pharmacy, have developed a nanotechnology approach that potentially could eliminate the problems of side effects and drug resistance in the treatment of cancer. Under traditional chemotherapy, cancer cells, like bacteria, can develop resistance to drug therapy, leading to a relapse of the disease.

As reported in the December 21, 2009, issue of the journal Small, He, Minko and their co-researchers, including investigators from Merck & Co. and Carl Zeiss SMT, a global nanotechnology firm, have designed nanomaterials that allow for the targeted and simultaneous delivery of a chemical drug to destroy cancer cells and a genetic drug to prevent drug resistance.

"We modified the surface of mesoporous silica nanoparticles so that an anticancer drug, doxorubicin, could be loaded into the pores of the silica nanoparticles. Also loaded onto the nanoparticles was a genetic drug designed to prevent or remove multidrug resistance outside the nanoparticles," explained He.

When administered to multidrug-resistant ovarian cancer cells, the nanoparticle treatment was more than 130 times more lethal than when doxorubicin was administrated alone . Most importantly, "the drug can only be released when it is inside the cancer cells. This controlled internal release mechanism can dramatically eliminate side effects associated with anticancer drugs to normal tissues," He noted.

Battling Aggressive Breast Cancer with Nanotubes

In related research, Professor He and another team of co-researchers have developed single-walled carbon nanotubes, consisting of cylinders of carbon about a nanometer in length, that hold the potential of providing a more effective means for detecting and selectively destroying aggressive breast cancer cells.

In a paper published in BMC Cancer late last year, the researchers showed that by chemically bonding a special antibody onto the nanotubes and taking advantage of two unique optical properties of carbon nanotubes (strong Raman scattering and near infrared absorption), single cancer cells can be detected and selectively eradicated while leaving the nearby normal cells unharmed. A uniqueness of this approach is that it offers the advantage of being more easily extended to other types of cancer cells. He's research in the areas of cancer detection and treatment is funded in part with grants from the National Science Foundation and National Cancer Institute.

Research Focuses on Practical Applications Across a Wide Range of Fields

The application of He's nanotechnology research is far and wide. In other research, He and members of her lab at Rutgers are working on the practical application of nanomaterials as a molecular diagnostic tool for Parkinson's disease. Other research is focused on the development of a platform to detect the presence of chemical warfare agents for homeland defense. And in yet other research, He and her lab members are working on nanotechnology to precisely and selectively measure iron ions (Fe3+) in remote ocean atmosphere dust and sea water, which is critical for the study of greenhouse gases and climate change .

At Rutgers, He teaches an undergraduate course in analytical chemistry and graduate courses in electrochemical analytical chemistry and a new course she designed in scanning probe microscopy. She is the recipient of the 2009 Rutgers Presidential Fellowship for Teaching Excellence.

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For more information: To learn more about He's research, visit http://andromeda.rutgers.edu/~huixinhe/huixinhe.html.

Source: Physorg.com - http://www.physorg.com/news186338960.html
Provided by Rutgers University (web)

(NanoRealm) - One of the difficulties of fighting cancer is that drugs often hit other non-cancerous cells, causing patients to get sick. But what if researchers could sneak cancer-fighting particles into just the cancer cells? Researchers at the Georgia Institute of Technology and the Ovarian Cancer Institute are working on doing just that. In the online journal BMC Cancer they detail a method that uses hydrogels - less than 100 nanometers in size - to sneak a particular type of small interfering RNA(siRNA) into cancer cells. Once in the cell the siRNA turns on the programmed cell death the body uses to kill mutated cells and help traditional chemotherapy do it’s job.

Many cancers are characterized by an over abundance of epidermal growth factor receptors (EGFR). When the EGFR level in a cell is elevated it tells the cell to replicate at a rapid rate. It also turns down apoptosis, or programmed cell death.

“With our technique we’re inhibiting EGFR’s growth, with small interfering RNA. And by inhibiting it’s growth, we’re increasing the cells’s apoptotic function. If we hit the cell with chemotherapy at the same time, we should be able to kill the cancer cells more effectively,” said John McDonald, professor at the School of Biology at Georgia Tech and chief research scientist at the Ovarian Cancer Institute.

Small interfering RNA is good at shutting down EGFR production, but once inside the cell siRNA has a limited life span. Keeping it protected inside the hydrogel nanoparticles allows them to get into the cancer cell safely and acts as a protective barrier around them. The hydrogel releases only a small amount of siRNA at a time, ensuring that while some are out in the cancer cell doing their job, reinforcements are held safely inside the nanoparticle until it’s time to do their job.

“It’s like a Trojan horse,” said L. Andrew Lyon, professor in the School of Chemistry and Biochemistry at Georgia Tech. “We’ve decorated the surface of these hydrogels with a ligand that tricks the cancer cell into taking it up. Once inside, the particles have a slow release profile that leaks out the siRNA over a timescale of days, allowing it to have a therapeutic effect.”

Cells use the messenger RNA (mRNA) to generate proteins, which help to keep the cell growing. Once the siRNA enters the cell, it binds to the mRNA and recruits proteins that attack the siRNA-mRNA complex. But the cancer cell's not finished; it keeps generating proteins, so without a continuous supply of siRNA, the cell recovers. Using the hydrogel to slowly release the siRNA allows it to keep up a sustained attack so that it can continue to interrupt the production of proteins.

“We’ve shown that you can get knock down out to a few days time frame, which could present a clinical window to come in and do multiple treatments in a combination chemotherapy approach,” said Lyon.

“The fact that this system is releasing the siRNA slowly, without giving the cell time to immediately recover, gives us much better efficiency at killing the cancer cells with chemotherapy,” added McDonald.

Previous techniques have involved using antibodies to knock down the proteins.
“But oftentimes, a mutation may arise in the targeted gene such that the antibody will no longer have the effect it once did, thereby increasing the chance for recurrence,” said McDonald.

The team used hydrogels because they’re non-toxic, have a relatively slow release rate, and can survive in the body long enough to reach their target.

“It’s a well-defined architecture that you’re using the intrinsic porosity of that material to load things into, and since our particles are about 98 percent water by volume, there’s plenty of internal volume in which to load things,” said Lyon.

Currently, the tests have been shown to work in vitro, but the team will be initiating tests in vivo shortly.

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Provided by Georgia Institute of Technology

The Georgia Institute of Technology is one of the nation's premier research universities. Ranked seventh among U.S. News & World Report's top public universities, Georgia Tech's more than 20,000 students are enrolled in its Colleges of Architecture, Computing, Engineering, Liberal Arts, Management and Sciences. Tech is among the nation's top producers of women and minority engineers. The Institute offers research opportunities to both undergraduate and graduate students and is home to more than 100 interdisciplinary units plus the Georgia Tech Research Institute.

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Source: PhyOrg.com (web)

(NanoRealm)- University of Florida scientists have developed a new nanoparticle that could improve cancer detection and drug delivery. The particle, called a “micelle” and made up of a cluster of molecules called aptamers, easily recognizes tumors and binds strongly to them. It also has properties that allow it to easily get inside cells for intracellular studies and drug delivery.

“That is important, because we could attach a drug to the aptamer so that the drug could get into a cell,” said Yanrong Wu, who recently completed her doctoral research at UF. Wu was the first author of a paper describing the findings in January in the Proceedings of the National Academy of Sciences entitle "DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells".


In allowing more targeted treatment of diseased cells, the micelles would help reduce damage to healthy cells even with large doses of chemotherapy. Current methods often destroy normal cells while trying to kill tumor cells.

In biological studies, molecules termed “probes” have properties that enable them to detect other molecules or organisms of interest, such as viruses. Compared with existing probes such as antibodies, the aptamers offer advantages in terms of ease of production and identification, faster response time and much lower molecular weight.

Aptamers, the building blocks of the micelles, are short single strands of DNA that can recognize other molecules based on certain chemical conformation.

In previous drug delivery tests, aptamers on their own could only attach limited drug molecules and sometimes could not effectively recognize tumor cells, so UF researchers re-engineered the molecule to improve its usefulness in biomedical studies in the watery environment inside the body.

They effectively turned the aptamer molecules into a molecular recognition and drug delivery system combination that escorts water-insoluble compounds such as drugs into cells by encapsulating them inside a water-soluble structure.

To do so, the team, led by Weihong Tan, the V.T. and Louise Jackson professor of chemistry at the College of Liberal Arts and Sciences and a professor of physiology and functional genomics in the UF College of Medicine, attached a “water-hating” — or hydrophobic — tail to the aptamers. The new molecules cluster together to form a micelle by tucking their water-hating tails together, exposing only the “water-loving” — or hydrophilic — portion of the structure. In that way, the micelle can shield water-insoluble agents such as drugs within its center, and help usher them into cells.

“It was kind of a stealth situation where the cell sees only the hydrophilic part, but inside, the drug is in the hydrophobic part,” said Nick Turro, the William P. Schweitzer professor of chemistry at Columbia University, who was not involved in the study. “This opens a number of avenues that were unavailable before.”
In tests that mimic physiological conditions, the micelles were more sensitive than the molecular probes alone. The micelle bound more strongly to target cells. That could lead to easier and earlier detection of biomarkers of disease such as cancer.

“When you are talking about diagnosis, these aptamers in micelles will have a much higher signal than individual aptamers, so we may be able to detect very small amounts of the substance we’re testing for,” said Tan, also a member of the UF Genetics Institute, the UF Shands Cancer Center and the Moffitt Cancer Center and Research Institute.

The micelle structures also might prove useful to more accurately determine how much diseased tissue is left behind after chemotherapy or surgery.

Now that the researchers have demonstrated the micelle’s ability to bind in simulated physiological conditions, the next step will be to test it in real tumors.

The National Institutes of Health and The Florida Biomedical Research Program supported the research. Other investigators include Haipeng Liu, Kwame Sefah and Ruowen Wang.

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Source: University of Florida (news)

Scientists from the U.S. Department of Energy's Argonne National Laboratory and the University of Chicago Medical Center are shaking up the world of materials science and cancer research on the cover of the February 2010 issue of the journal Nature Materials.

Brain cancer is notoriously difficult to treat with standard cancer-fighting methods, so scientists have been looking outside standard medicine and into nanomaterials as a treatment alternative.

"Our mission is to develop advanced 'smart' materials with unique properties," said Elena Rozhkova, a nanoscientist with Argonne's Center for Nanoscale Materials. "These efforts are directed to the improvement of the national quality of life, including creating novel medical technologies."

A team of scientists, including Rozhkova, Dong-Hyum Kim, Valentyn Novosad, Tijana Rajh and Samuel Bader from Argonne, and Maciej Lesniak and Ilya Ulasov from the University of Chicago Brain Tumor Center, developed a technique that uses gold-plated iron-nickel microdiscs connected to brain-cancer-seeking antibodies to fight cancer. The microdiscs are an example of a nanomagnetic material and can be used to probe cell mechanics and activate mechanosensitive ion channels, as well as to advance cancer therapies.
The discs posses a spin-vortex ground state and sit dormant on the cancer cell until a small alternating magnetic field is applied and the vortices shift, creating an oscillation. The energy from the oscillation is transferred to the cell and triggers apoptosis, or "cell suicide."
Since the antibodies are attracted only to brain cancer cells, the process leaves surrounding healthy cells unharmed. This makes them unlike traditional cancer treatment methods, such as chemotherapy and radiation, which negatively affect both cancer and normal healthy cells.


"We are very excited about this melding of materials and life sciences, but we are still in the very early research stages," materials scientist Valentyn Novosad said. "We are planning to begin testing in animals soon, but we are several years away from human trials. Everything is still experimental."

Along with continued testing and research of the treatment, scientists also have to examine any possible side effects that have been so far unseen in the laboratory.

"The use of nanomaterials for cancer treatment is not a new concept, but the ability to kill the cells without harming surrounding healthy cells has incredible potential," Rozhkova said. "Such a topic can only be approached with the expertise of markedly differing disciplines such as physics, chemistry, biology and nanotechnology and can make a great impact in important areas of science and modern advanced technologies."

Source: Argone National Laboratory; Science Daily

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Information of Argone National Laboratory:
Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America 's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.

A world-renowned medical researcher discusses the key role that nanotechnology has begun to play in the detection and treatment of cancer in an article that will appear in the March 2010 edition of Mechanical Engineering magazine.

Mauro Ferrari, Ph.D., explains how advanced nanotech-based therapeutic agents possess characteristics that can effectively exploit the unique mechanical properties of cancer lesions and treat the various forms of the disease locally.

According to Ferrari, professor and chairman of the Department of Nanomedicine and Biomedical Engineering at The University of Texas Health Science Center, some engineered nano-particles have demonstrated the capability to deliver drugs only to areas affected by disease, in the process protecting healthy cells and reducing debilitating side effects.


An important insight in understanding how to treat cancer, Ferrari says, is that aspects of the disease such as malignancy, metastasis, and angiogenesis (which is the growth of new arteries to feed tumors) are mechanical phenomena pertaining to the motion and transport of blood and cells. Nanotechnology-based therapies currently under experimentation for cancer treatment take advantage of some of these mechanical properties to find new ways to attack tumors.

This constitutes a new field that Ferrari and his medical colleagues refer to as “transport oncophysics.”

Formulations of drugs made from nano-particles have shown the ability to overcome biological barriers -- for example, by leaking through the blood vessels inside a tumor -- to concentrate on localized cancers. Because of this, nanotechnology-based drugs may be used in smaller doses and are less likely to disperse to healthy parts of the body. Ferrari and his team at The University of Texas also have designed nano-particles called Multi-Stage Vectors, which offer great promise in targeting individual cancer cells.

“We are on the brink of a new era in cancer treatment,” asserts Ferrari in the forthcoming article, titled “Infernal Mechanism.”

“The level of specificity that can be achieved through the use of the conceptual model of cancer as a mechanical disease – and through the power of the mechanical engineering design process – will result in greater therapeutic efficacy with reduced side effects,” he concludes.

Mauro Ferrari will speak on Feb. 8 at the First Global Congress on Nano-engineering for Medicine and Biology. The conference, sponsored by ASME, will open on Feb. 7 at the JW Marriott Houston, in Houston, Texas.

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Above information was sourced from ASME.

About ASME
ASME helps the global engineering community develop solutions to real world challenges. Founded in 1880 as the American Society of Mechanical Engineers, ASME is a not-for-profit professional organization that enables collaboration, knowledge sharing and skill development across all engineering disciplines, while promoting the vital role of the engineer in society. ASME codes and standards, publications, conferences, continuing education and professional development programs provide a foundation for advancing technical knowledge and a safer world.