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.
The tumors of treated rabbits were also permeated with more immune cells than those of the control rabbits. Patrick Winter, research assistant professor of medicine and biomedical engineering at Washington University and lead author of the study, says this may mean the body’s ability to recognize a tumor as foreign and mount an attack is somehow amplified by the treatment.
Because the formation of new blood vessels is an essential component of tumor growth, Winter believes his team’s approach will be highly adaptable. “A method to block angiogenesis should be very effective in a wide range of cancers,” he says.
By including an imaging molecule, the researchers were able to noninvasively create detailed three-dimensional maps of the tumors’ vasculature, a feat never before achieved. They hope this will allow them to track how tumor-feeding blood vessels respond to various treatments, and to better understand tumor vasculature in general.
In fact, nanoparticles strictly designed for imaging–loaded with the metallic compound but not with any drug—will be the first application of the new technology to be tested in humans. Winter anticipates human clinical trials will begin by the end of 2008. Clinical trials of drug-laden nanoparticles may be three to five years away.
The Washington University team is one of many groups investigating nanoparticle-based systems for treating and imaging cancer, which range from elaborate polymers to quantum dots and use a wide range of mechanisms to deliver their effects. While many of these second- generation nanoparticle approaches show great promise in animal models, none have yet progressed to human clinical trials. In many cases, the safety of the nanoparticles’ components has yet to be demonstrated. Winters believes his group’s approach may circumvent some of these safety concerns, as the liquid core of the new nanoparticles has been previously used in artificial blood. “The toxicology and distribution and elimination of these agents is already very well known,” he says. “And these agents have already been used in large-scale manufacturing processes.”