chemotherapy drugs are like a shotgun. Although doctors are only intended for tumors, the compounds hit a variety of other places in the body, leading to effects such as damage to the bone marrow and the side hair loss. To improve their goal, researchers have tried to pack these drugs inside small hollow nano-sized containers that can be directed to tumors and bypass healthy tissue. But the size, shape, and composition of these "nanoparticles" can affect considerably when and where they are taken. Now, scientists have identified the landscape of some 100 different formulations of nanoparticles and found that when a conventional chemotherapeutic drug is packaged in the best of these nanoparticles, it is much more effective against prostate cancer in animals the single drug.
The new findings are the first to show promise of therapeutic nanoparticles against cancer. Nearly a dozen of these tiny drug carriers are already in clinical trials. But researchers are still struggling to adjust the size and composition of nanoparticles that work best for conveying drugs to tumors. So for their study, a team of 30 researchers led by chemical engineer Robert Langer of the Massachusetts Institute of Technology in Cambridge, physician-researcher Omid Farokhzad of Harvard Medical School, and biochemical engineer Stephen Zale BIND Biosciences in Cambridge, Massachusetts, decided to adopt a more systematic approach.
Rather than looking at all types of biomaterials from which their particles, the researchers started with six different already approved materials for use by the Food and Drug Administration of the United States, as well as freight anticancer compound already approved called docetaxel. Then they ranged from 10 different factors, including the particle size in which they trapped docetaxel, the density of chemical groups used to wrap the particles of the immune system, additional surface-active compounds used to target the particles to tumor cells interest, the amount of docetaxel they wore, and how fast the particles decomposed and released their cargo.
After a preliminary assessment of more than 100 different drugs nanoparticle formulations, Langer and colleagues installed on a design containing particles of 100 nanometers made from a combination of a biodegradable polymer known as name PLA and a coating of PEG, other polymer which readily binds water molecules and helps hide the particles of the immune system. Some of the PEG chains were also capped with copies of a small molecule called ACUPA which binds to the receptor molecules overexpressed on the surface of cancer cells in the prostate.
Tests on mice, rats and monkeys have shown that delivering docetaxel in nanoparticles produced plasma drug concentrations over a period of 24 hours at 100 times higher than standard docetaxel injections made; 10 times more drug accumulated in tumors, as well. And in an early clinical safety trial of 17 people, the researchers found the drug accumulation in tumors and clinical effects at doses as low as 20% of the docetaxel dose normally prescribed, as they report online today Science Translational Medicine . Additional clinical trials are now testing higher doses, and no new toxicities have been observed to date.
"It is an important result and a great direction to go in," said Joseph DeSimone, an expert chemist and drug nanoparticle at the University of North Carolina, Chapel Hill. The study shows that delivering drugs within nanoparticles has the potential to improve the effectiveness of many conventional anticancer drugs and other therapeutic agents that are limited by side effects, he said: "When you change where the deposition of the drug, you basically change the outcome. "
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