This blog is all about current FDA approved drugs to treat the hepatitis C virus (HCV) with a focus on treating HCV according to genotype, using information extracted from peer-reviewed journals, liver meetings/conferences, and interactive learning activities.
Risk Of Developing Liver Cancer After HCV Treatment
In new study published in PNAS, scientists found that nanoparticles, produced from chemicals in tea, reduced tumors by 80 percent.
July 16, 2012
Currently, large doses of chemotherapy are required when treating certain forms of cancer, resulting in toxic side effects. The chemicals enter the body and work to destroy or shrink the tumor, but also harm vital organs and drastically affect bodily functions. Now, University of Missouri scientists have found a more efficient way of targeting prostate tumors by using gold nanoparticles and a compound found in tea leaves.
This new treatment would require doses that are thousands of times smaller than chemotherapy and do not travel through the body inflicting damage to healthy areas. The study is being published in the Proceedings of the National Academy of Science. Full Story
These posts, made of carbon nanotubes, can trap cancer cells and other tiny objects as they flow through a microfluidic device. Each post is 30 microns in diameter.
Image: Brian Wardle
Catching cancer with carbon nanotubes
New device to test blood can spot cancer cells, HIV on the fly
A Harvard bioengineer and an MIT aeronautical engineer have created a new device that can detect single cancer cells in a blood sample, potentially allowing doctors to quickly determine whether cancer has spread from its original site.
The microfluidic device, described in the March 17 online edition of the journal Small, is about the size of a dime, and could also detect viruses such as HIV. It could eventually be developed into low-cost tests for doctors to use in developing countries where expensive diagnostic equipment is hard to come by, says Mehmet Toner, professor of biomedical engineering at Harvard Medical School and a member of the Harvard-MIT Division of Health Sciences and Technology.
Toner built an earlier version of the device four years ago. In that original version, blood taken from a patient flows past tens of thousands of tiny silicon posts coated with antibodies that stick to tumor cells. Any cancer cells that touch the posts become trapped. However, some cells might never encounter the posts at all.
Toner thought if the posts were porous instead of solid, cells could flow right through them, making it more likely they would stick. To achieve that, he enlisted the help of Brian Wardle, an MIT associate professor of aeronautics and astronautics, and an expert in designing nano-engineered advanced composite materials to make stronger aircraft parts.
Out of that collaboration came the new microfluidic device, studded with carbon nanotubes, that collects cancer cells eight times better than the original version.
Captured by nanotubes
Circulating tumor cells (cancer cells that have broken free from the original tumor) are normally very hard to detect, because there are so few of them — usually only several cells per 1-milliliter sample of blood, which can contain tens of billions of normal blood cells. However, detecting these breakaway cells is an important way to determine whether a cancer has metastasized.
“Of all deaths from cancer, 90 percent are not the result of cancer at the primary site. They’re from tumors that spread from the original site,” Wardle says.
When designing advanced materials, Wardle often uses carbon nanotubes — tiny, hollow cylinders whose walls are lattices of carbon atoms. Assemblies of the tubes are highly porous: A forest of carbon nanotubes, which contains 10 billion to 100 billion carbon nanotubes per square centimeter, is less than 1 percent carbon and 99 percent air. This leaves plenty of space for fluid to flow through.
The MIT/Harvard team placed various geometries of carbon nanotube forest into the microfluidic device. As in the original device, the surface of each tube can be decorated with antibodies specific to cancer cells. However, because the fluid can go through the forest geometries as well as around them, there is much greater opportunity for the target cells or particles to get caught.
The researchers can customize the device by attaching different antibodies to the nanotubes’ surfaces. Changing the spacing between the nanotube geometric features also allows them to capture different sized objects — from tumor cells, about a micron in diameter, down to viruses, which are only 40 nm.
The researchers are now beginning to work on tailoring the device for HIV diagnosis. Toner’s original cancer-cell-detecting device is now being tested in several hospitals and may be commercially available within the next few years.
Rashid Bashir, director of the Micro and Nanotechnology Laboratory at the University of Illinois at Urbana-Champaign, says that the ability to filter specific particles, cells or viruses from a blood sample so they can be analyzed is a critical step towards creating handheld diagnostic devices.
“Anything you can do to improve capture efficiency, or anything novel you can do to get the particles to interact with a surface more effectively, will help with sample preparation,” says Bashir, who was not part of the research team.
Cancer's side effects can be lessened with nanoparticles
10, January 2011.
Researchers at MIT and Brigham and Women's Hospital have shown that they can deliver the cancer drug cisplatin much more effectively and safely in a form that has been encapsulated in a nanoparticle targeted to prostate tumor cells and is activated once it reaches its target.
Using the new particles, the researchers were able to successfully shrink tumors in mice, using only one-third the amount of conventional cisplatin needed to achieve the same effect. That could help reduce cisplatin’s potentially severe side effects, which include kidney damage and nerve damage.
In 2008, the researchers showed that the nanoparticles worked in cancer cells grown in a lab dish. Now that the particles have shown promise in animals, the team hopes to move on to human tests.
“At each stage, it’s possible there will be new roadblocks that will come up, but you just keep trying,” says Stephen Lippard, the Arthur Amos Noyes Professor of Chemistry and a senior author of the paper, which appears in the Proceedings of the National Academy of Sciences the week of Jan. 10.
Omid Farokhzad, associate professor at Harvard Medical School and director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s Hospital, is also a senior author of the paper. Shanta Dhar, a postdoctoral associate in Lippard’s lab, and Nagesh Kolishetti, a postdoctoral associate in Farokhzad’s lab, are co-lead authors.
Better delivery Cisplatin, which doctors began using to treat cancer in the late 1970s, destroys cancer cells by cross-linking their DNA, which ultimately triggers cell death. Despite its adverse side effects, which also include nerve damage and nausea, about half of all cancer patients receiving chemotherapy are taking Cisplatin or other platinum drugs.
Another problem with conventional cisplatin is its relatively short lifetime in the bloodstream. Only about 1 percent of the dose given to a patient ever reaches the tumor cells’ DNA, and about half of it is excreted within an hour of treatment.
To prolong the time in circulation, the researchers decided to encase a derivative of cisplatin in a hydrophobic (water-repelling) nanoparticle. First, they modified the drug, which is normally hydrophilic (water-attracting), with two hexanoic acid units — organic fragments that repel water. That enabled them to encapsulate the resulting prodrug — a form that is inactive until it enters a target cell — in a nanoparticle.
Using this approach, much more of the drug reaches the tumor, because less of the drug is degraded in the bloodstream. The researchers found that the nanoparticles circulated in the bloodstream for about 24 hours, at least 5 times longer than un-encapsulated cisplatin. They also found that it did not accumulate as much in the kidneys as conventional cisplatin. To help the nanoparticles reach their target, the researchers also coated them with molecules that bind to PSMA (prostate specific membrane antigen), a protein found on most prostate cancer cells.
After showing the nanoparticles’ improved durability in the blood, the researchers tested their effectiveness by treating mice implanted with human prostate tumors. They found that the nanoparticles reduced tumor size as much as conventional cisplatin over 30 days, but with only 30 percent of the dose.
“They have very elegantly showed not just improved efficacy but also decreased toxicity,” says Mansoor Amiji, chair of pharmaceutical sciences at Northeastern University’s Bouvé College of Health Sciences, who was not involved in the research. “With a nanoparticle, you should be able to get higher doses into the patient, so you can have a much better therapeutic result and not worry as much about side effects.”
This type of nanoparticle design could be easily adapted to carry other types of drugs, or even more than one drug at a time, as the researchers reported in a PNAS paper last October. They could also be designed to target tumors other than prostate cancer, as long as those tumors have known receptors that could be targeted. One example is the Her-2 receptor abundant in some types of breast cancer, says Lippard.
The particles tested in this paper are based on the same design as particles developed by Farokhzad and MIT Institute Professor Robert Langer that deliver the cancer drug docetaxel. A Phase I clinical trial to assess those particles began last week, run by BIND Biosciences. Additional animal testing is needed before the cisplatin-carrying particles can go into human clinical trials, says Farokhzad. “At the end of the day, if the development results are all promising, then we would hope to put something like this in humans within the next three years,” he says.
This story is republished courtesy of MIT News (http://web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.
More information: "Targeted delivery of cisplatin prodrug for safer and more effective prostate cancer therapy in vivo," by Shanta Dhar, Nagesh Kolishetti, Stephen J. Lippard, and Omid C. Farokhzad. Proceedings of the National Academy of Sciences, 10, January 2011. Provided by Massachusetts Institute of Technology (news : web)
Nanoparticles have a unique ability to target cancer cells and wipe out tumors. At Brigham and Womens Hospital, development of these new technologies holds tremendous promise for cancer treatment.
