Nanotechnology a 'green' approach to treating liver cancer

Nanotechnology a 'green' approach to treating liver cancer

Minimally invasive procedure targets, destroys precancerous cells in mice
University of Missouri-Columbia

According to the American Cancer Society, more than 700,000 new cases of liver cancer are diagnosed worldwide each year. Currently, the only cure for the disease is to surgically remove the cancerous part of the liver or transplant the entire organ. However, an international study led by University of Missouri School of Medicine researchers has proven that a new minimally invasive approach targets and destroys precancerous tumor cells in the livers of mice and in vitro human cells.

"The limitations when treating most forms of cancer involve collateral damage to healthy cells near tumor sites," said Kattesh Katti, Ph.D., Curators' Professor of Radiology and Physics at the MU School of Medicine and lead author of the study. "For more than a decade we have studied the use of nanotechnology to test whether targeted treatments would reduce or eliminate damage to nearby healthy cells. Of particular interest has been the use of green nanotechnology approaches pioneered here at MU that use natural chemical compounds from plants."

The study was conducted in the United States and Egypt, and it involved the use of gold nanoparticles encapsulated by a protective stabilizer called gum Arabic. The nanoparticles were introduced to the livers of mice intravenously and were heated with a laser through a process known as photothermal therapy.

"Gum Arabic is a natural gum made of the hardened sap from acacia trees," said Katti, who also serves as director of the MU Institute of Green Nanotechnology and is the Margaret Proctor Mulligan Distinguished Professor of Medical Research at the MU School of Medicine. "It is FDA-approved for human consumption and is primarily used in the food industry as an additive. It also promotes adhesion of gold nanoparticles engineered to attract to precancerous and malignant cells - which are much more susceptible to lower levels of heat than healthy cells. Once the nanoparticles travel and adhere to cancerous cells, they are heated to a temperature that destroys them but leaves healthy tissue unaffected."

Katti's team studied a total of 224 mice. Half were identified as having precancerous cells in their livers. The other half had normal liver tissue. Outside of the control group, the mice received either an intravenous injection of gum Arabic alone or gum Arabic-encapsulated gold nanoparticles with or without laser therapy.

"The administration of gum Arabic, gold nanoparticles and photothermal therapy caused no change to healthy tissue, which confirmed the safe use of these treatments," Katti said. "However, the use of gum Arabic-encapsulated nanoparticles combined with photothermal therapy resulted in the targeted eradication of the precancerous cells and their genetic code in both our mice model and the human in vitro cell model we developed for this study."

Katti said the next step for further developing the technique into a cancer treatment for humans will be a clinical trial.

"The components for this new therapy are inexpensive, do not have any issues associated with a shelf-life and are easy to produce," Katti said. "Most importantly, it does not involve the use of harsh chemotherapy drugs or radiation. It is a 'green' approach that also may lead to successful treatment of other forms of cancer."

The study, "Photothermal Therapy Mediated by Gum Arabic-conjugated Gold Nanoparticles Suppresses Liver Preneoplastic Lesions in Mice," recently was published in the Journal of Photochemistry and Photobiology B: Biology. Co-authors from the research group include Menka Khoobchandani, Ph.D.; Sagar Gupta, Ph.D.; Kavita Katti, Ph.D.; and Ravi Shukla, Ph.D. Support for the study was provided by the MU School of Medicine, the MU Interdisciplinary Intercampus Research Program and the National Research Centre in Cairo, Egypt.

About the MU School of Medicine
The MU School of Medicine has improved health, education and research in Missouri and beyond for more than 165 years. MU physicians treat patients from every county in the state, and more Missouri physicians received their medical degrees from MU than from any other university. For more information, visit http://medicine.missouri.edu/.

IMAGE: Kattesh Katti, Ph.D., Curators' Professor of Radiology and Physics at the MU School of Medicine and lead author of the study.

Credit: Justin Kelley, MU Health

New study shows promise in using RNA nanotechnology to treat cancers and viral infections

New study shows promise in using RNA nanotechnology to treat cancers and viral infections

The research team on this study includes (L-R) Markey Cancer Center Director Dr. Mark Evers, Farzin Haque, Dr. Piotr Rychahou, Yi Shu, Dan Shu and Peixuan Guo.



LEXINGTON, Ky. (Sept. 4, 2012) — A new study by University of Kentucky researchers shows promise for developing ultrastable RNA nanoparticles that may help treat cancer and viral infections by regulating cell function and binding to cancers without harming surrounding tissue.

The study, published in Nano Today, was carried out in the laboratory of Peixuan Guo, the William S. Farish Endowed Chair in Nanobiotechnology at the UK Markey Cancer Center, in collaboration with Dr. Mark Evers, director of the UK Markey Cancer Center.

The study uses RNA (ribonucleic acid) as a building block for the bottom-up fabrication of nanostructures. Using the RNA nanotechnology pioneered by Guo, the researchers constructed ultrastable X-shaped RNA nanoparticles using re-engineered RNA fragments to carry up to four therapeutic and diagnostic modules. Their RNA nanoparticles can include small interfering RNA for silencing genes, micro-RNA for regulating gene expression, aptamer for targeting cancer cells, or a ribozyme that can catalyze chemical reactions.

The study demonstrated that regulation of cellular functions progressively increased with the increasing number of functional modules in the nanoparticle.

"RNA nanotechnology is an emerging field, but the instability and degradation of RNA nanoparticles have made many scientists flinch away from the research in RNA nanotechnology," Guo said. "We have addressed these issues, and now it is possible to produce RNA nanoparticles that are highly stable both chemically and thermodynamically in the test tube or in the body with great potential as therapeutic reagents."

The RNA nanoparticles displayed several favorable attributes: polyvalent nature, which allows simultaneous delivery of multiple functional molecules for achieving synergistic effects; modular design, which enables controlled self-assembly with defined structure; thermodynamically stable, which keeps the RNA nanoparticles intact in animal and human circulation systems, where they exist at very low concentrations; and chemically stable, which makes the nanoparticles resistant to RNase (an enzyme, which cleaves RNA) digestion in the blood serum.

"A major problem with cancer treatments is the ability to more directly and specifically deliver anti-cancer drugs to cancer metastases," Evers said. "Using the nanotechnology approach that Peixuan Guo and his group have devised may allow us to more effectively treat cancer metastasis with fewer side effects compared to current chemotherapy."

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In addition to Evers and Markey team member Dr. Piotr Rychahou, Guo's research team at UK also includes Farzin Haque, first author on the paper; Dan Shu; Yi Shu; and Luda Shlyakhtenko.

Nanozyme shuts down production of hepatitis C virus in the body

UF researchers develop “nanorobot” that can be programmed to target different diseases

Monday, July 16, 2012.

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GAINESVILLE, Fla. — University of Florida researchers have moved a step closer to treating diseases on a cellular level by creating a tiny particle that can be programmed to shut down the genetic production line that cranks out disease-related proteins.

In laboratory tests, these newly created “nanorobots” all but eradicated hepatitis C virus infection. The programmable nature of the particle makes it potentially useful against diseases such as cancer and other viral infections.

The research effort, led by Y. Charles Cao, a UF associate professor of chemistry, and Dr. Chen Liu, a professor of pathology and endowed chair in gastrointestinal and liver research in the UF College of Medicine, is described online this week in the Proceedings of the National Academy of Sciences.

“This is a novel technology that may have broad application because it can target essentially any gene we want,” Liu said. “This opens the door to new fields so we can test many other things. We’re excited about it.”

During the past five decades, nanoparticles — particles so small that tens of thousands of them can fit on the head of a pin — have emerged as a viable foundation for new ways to diagnose, monitor and treat disease. Nanoparticle-based technologies are already in use in medical settings, such as in genetic testing and for pinpointing genetic markers of disease. And several related therapies are at varying stages of clinical trial.

The Holy Grail of nanotherapy is an agent so exquisitely selective that it enters only diseased cells, targets only the specified disease process within those cells and leaves healthy cells unharmed.

To demonstrate how this can work, Cao and colleagues, with funding from the National Institutes of Health, the Office of Naval Research and the UF Research Opportunity Seed Fund, created and tested a particle that targets hepatitis C virus in the liver and prevents the virus from making copies of itself.
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Hepatitis C infection causes liver inflammation, which can eventually lead to scarring and cirrhosis.

The disease is transmitted via contact with infected blood, most commonly through injection drug use, needlestick injuries in medical settings, and birth to an infected mother. More than 3 million people in the United States are infected and about 17,000 new cases are diagnosed each year, according to the Centers for Disease Control and Prevention. Patients can go many years without symptoms, which can include nausea, fatigue and abdominal discomfort.

Current hepatitis C treatments involve the use of drugs that attack the replication machinery of the virus. But the therapies are only partially effective, on average helping less than 50 percent of patients, according to studies published in The New England Journal of Medicine and other journals. Side effects vary widely from one medication to another, and can include flu-like symptoms, anemia and anxiety.

Cao and colleagues, including graduate student Soon Hye Yang and postdoctoral associates Zhongliang Wang, Hongyan Liu and Tie Wang, wanted to improve on the concept of interfering with the viral genetic material in a way that boosted therapy effectiveness and reduced side effects.

The particle they created can be tailored to match the genetic material of the desired target of attack, and to sneak into cells unnoticed by the body’s innate defense mechanisms.

Recognition of genetic material from potentially harmful sources is the basis of important treatments for a number of diseases, including cancer, that are linked to the production of detrimental proteins. It also has potential for use in detecting and destroying viruses used as bioweapons.

The new virus-destroyer, called a nanozyme, has a backbone of tiny gold particles and a surface with two main biological components. The first biological portion is a type of protein called an enzyme that can destroy the genetic recipe-carrier, called mRNA, for making the disease-related protein in question. The other component is a large molecule called a DNA oligonucleotide that recognizes the genetic material of the target to be destroyed and instructs its neighbor, the enzyme, to carry out the deed. By itself, the enzyme does not selectively attack hepatitis C, but the combo does the trick.
“They completely change their properties,” Cao said.

In laboratory tests, the treatment led to almost a 100 percent decrease in hepatitis C virus levels. In addition, it did not trigger the body’s defense mechanism, and that reduced the chance of side effects. Still, additional testing is needed to determine the safety of the approach.

Future therapies could potentially be in pill form.

“We can effectively stop hepatitis C infection if this technology can be further developed for clinical use,” said Liu, who is a member of The UF Shands Cancer Center.

The UF nanoparticle design takes inspiration from the Nobel prize-winning discovery of a process in the body in which one part of a two-component complex destroys the genetic instructions for manufacturing protein, and the other part serves to hold off the body’s immune system attacks. This complex controls many naturally occurring processes in the body, so drugs that imitate it have the potential to hijack the production of proteins needed for normal function. The UF-developed therapy tricks the body into accepting it as part of the normal processes, but does not interfere with those processes.

“They’ve developed a nanoparticle that mimics a complex biological machine — that’s quite a powerful thing,” said nanoparticle expert Dr. C. Shad Thaxton, an assistant professor of urology at the Feinberg School of Medicine at Northwestern University and co-founder of the biotechnology company AuraSense LLC, who was not involved in the UF study. “The promise of nanotechnology is extraordinary. It will have a real and significant impact on how we practice medicine.”

http://news.ufl.edu/2012/07/16/nanobot/

Nanotechnology may lead to new treatment of liver cancer

Nanotechnology may lead to new treatment of liver cancer

February 21, 2011 (PhysOrg.com) -- Nanotechnology may open a new door on the treatment of liver cancer, according to a team of Penn State College of Medicine researchers. They used molecular-sized bubbles filled with chemotherapy drugs to prevent cell growth and initiate cell death in test tubes and mice.

Researchers evaluated the use of molecular-sized bubbles filled with C6-ceramide, called cerasomes, as an anti-cancer agent. Ceramide is a lipid molecule naturally present in the cell's plasma membrane and controls cell functions, including cell aging, or senescence.

Hepatocellular carcinoma is the fifth most common cancer in the world and is highly aggressive. The chance of surviving five years is less than five percent, and treatment is typically chemotherapy and surgical management including transplantation.

"The beauty of ceramide is that it is non-toxic to normal cells, putting them to sleep, while selectively killing cancer cells," said Mark Kester, Ph.D., G. Thomas Passananti Professor of Pharmacology.

Cerasomes, developed at Penn State College of Medicine, can target cancer cells very specifically and accurately, rather than affecting a larger area that includes healthy cells. The problem with ceramide is that as a lipid, it cannot be delivered effectively as a drug. To solve this limitation, the researchers use nanotechnology, creating the tiny cerasome, to turn the insoluble lipid into a soluble treatment.

"Cerasomes were designed as a therapeutic alternative to common chemotherapeutics," said Kester. "These have been shown to be toxic to cancer cells and not to normal cells, and have already been shown to effectively treat cellular and animal models of breast cancer and melanoma. Cerasomes have also been shown to be essentially free of toxic side effects normally associated with anticancer agents."

In the test tube and animal models of liver cancer, cerasomes, but not a placebo, selectively induced cell death in the cancer cells.

In mice with liver cancer, cerasomes blocked tumor vascularisation, the forming of blood vessels needed for growth and nutrition. Studies show that lack of nutrition causes cells to create more ceramide and leads to cell death.

"It is plausible that preventing liver tumor vascularization with cerasome treatment could induce widespread apoptosis, a genetically programmed series of events that leads to cell death in tumors," Kester said. "The efficacy of our cerasomes in the treatment of diverse cancers lends significant therapeutic promise as it translates from bench to bedside."

The researchers published their work in the journal Gut. A Penn State Dean’s Feasibility Grant, Pennsylvania tobacco settlement funds, and the National Institutes of Health supported this work.

In an earlier study published in the journal Blood, researchers observed that cerasome use led to complete remission in aggressive, large granular lymphocytic leukemia in rats. In addition, the protein survivin, which prevents cell death, is heavily produced in NK-leukemia cells, but not in normal cells. Cerasome decreased expression of survivin and may lead to a therapeutic approach for fatal leukemia.

Provided by Pennsylvania State University (news : web)
http://www.physorg.com/news/2011-02-nanotechnology-treatment-liver-cancer.html