Investigators from the Washington University School of Medicine in St. Louis have developed nanoparticles laden with fumagillin, an angiogenesis inhibitor, known to be extremely neurotoxic in systemic dose. When given to tumor-bearing rabbits, the nanoconstructs were shown to be very effective in suppressing the neovasculature and inhibiting adenocarcinoma development, in concentrations way below a toxic dose:
“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.
Senior author Gregory M. Lanza, M.D., Ph.D., associate professor of medicine and of biomedical engineering, and Samuel A. Wickline, M.D., professor of medicine, of physics and of biomedical engineering, are co-inventors of the nanoparticle technology. The nanoparticles measure only about 200 nanometers across, or 500 times smaller than the width of a human hair. Their cores are composed mostly of perfluorocarbon, a safe compound used in artificial blood.
The nanoparticles can be adapted to many different medical applications. In addition to carrying drugs to targeted locations, they can be manufactured to highlight specific targets in magnetic resonance imaging (MRI), nuclear imaging, CT scanning and ultrasound imaging.
Washington University School of Medicine in St. Louis: Nano-sized technology has super-sized effect on tumors…