Using nanotechnology to devise targeted drug delivery systems is one of the hottest research areas going, and another team added to the excitement last week. A new nanoparticle formulated to deliver a drug directly to the growing blood vessels that feed tumors — and help circumvent the crippling side effects associated with chemotherapy — has been developed by researchers at Washington University in Saint Louis. Several nanoparticle-based drugs are already approved to fight cancer, and many more are currently moving through human clinical trials. But these so-called “first generation” strategies tend to rely on passive or naturally occurring mechanisms to find their way to tumors. Recent efforts like the Washington University technology are focusing more on designing sophisticated nanodelivery systems that can be adapted for use with multiple drugs. The WU group is using a fungal drug called fumagillin, which stops the formation of new blood vessels in tumors by blocking the proliferation of endothelial cells that line blood vessel walls. Fumagillin is a powerful chemotherapeutic agent, but the dose needed to successfully suppress tumors causes intolerable neurotoxic side effects — a central limitation of many chemotherapy drugs. To target fumagillin directly at the blood vessels that feed a growing tumor, researchers adopted a nanoparticle platform they had previously developed for imaging growing blood vessels. The nanoparticles, about 250 nanometers in diameter, have inert liquid centers and an oily surface laced with two kinds of molecules — one for targeting and another for imaging. The targeting molecule latches onto a protein found in high concentrations on cells that line walls of new blood vessels, while the imaging molecule is a metallic substance that shows up on an MRI. To adapt the system for cancer treatment, they added fumagillin to the nanoparticles’ oily coatings. When injected into the bloodstream, the nanoparticles remain intact, protecting healthy tissues from absorbing their toxic payload. But when they reach the blood vessels feeding a tumor, their targeting molecules lock onto the surfaces of proliferating endothelial cells. Once attached, the particles’ lipid coats fuse with the cells’ lipid membranes and deliver the drug and the imaging molecule. The researchers used MRI to image the tumors in rabbits both before treatment and three hours after. They then dissected the tumors to confirm their size. Rabbits given the fully loaded nanoparticles had tumors that were drastically smaller than those of rabbits given nanoparticles either without the targeting molecule or without fumagillin. By delivering their cargo directly to the tumor site, the nanoparticles allowed the researchers to lower the required dose of fumagillin by a factor of 1,000. None of the rabbits displayed any detectable neurotoxic side effects. “I think it’s a very significant finding,” said Jolanta Kukowska-Latallo, research assistant professor of internal medicine at the University of Michigan and member of the Michigan Nanotechnology Institute for Medicine and Biological Sciences, who was not involved in the work. Go to: Technology Review

Posted April 23rd, 2008 under Innovation of the Week, Tech Transfer

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