A tumor treated with fumagillin nanoparticles (left) is smaller than an untreated tumor. Nanoparticles containing an image enhancing metal (yellow) show that the treated tumor has much less blood vessel growth than the untreated tumor. (Source: Washington University)

Researchers at Washington University School of Medicine in St. Louis have shown that chemotherapy doses can be dramatically reduced by focusing a powerful drug directly on tumors in rabbits using drug-coated nanoparticles. They found that a drug dose 1,000 times lower than used previously for this purpose markedly slowed tumor growth.

“Many chemotherapeutic drugs have unwanted side effects, and we’ve shown that our nanoparticle technology has the potential to increase drug effectiveness and decrease drug dose to alleviate harmful side effects,” says lead author Patrick M. Winter, Ph.D., research assistant professor of medicine and biomedical engineering.

The nanoparticles are extremely tiny beads of an inert, oily compound that can be coated with a wide variety of active substances. In an article published online in The FASEB Journal, the researchers describe a significant reduction of tumor growth in rabbits that were treated with nanoparticles coated with a fungal toxin called fumagillin. Human clinical trials have shown that fumagillin can be an effective cancer treatment in combination with other anticancer drugs.

In addition to fumagillin, the nanoparticles’ surfaces held molecules designed to stick to proteins found primarily on the cells of growing blood vessels. So the nanoparticles latched on to sites of blood vessel proliferation and released their fumagillin load into blood vessel cells. Fumagillin blocks multiplication of blood vessel cells, so it inhibited tumors from expanding their blood supply and slowed their growth.

Human trials have also shown that fumagillin can have neurotoxic side effects at the high doses required when given by standard methods. But the fumagillin nanoparticles were effective in very low doses because they concentrate where tumors create new blood vessels. The rabbits that received fumagillin nanoparticles showed no adverse side effects.

The nanoparticles will be tested this year in preliminary human clinical trials to determine the optimal method for using them as imaging agents. These studies will lay essential groundwork for using the nanoparticles as therapeutic agents.

Release Date: April 2, 2008
Source: Washington University

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Filed Under: Drug Discovery

 

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