Researchers Developing Targeted Cancer Therapy

Researchers at the Massachusetts Institute of Technology have taken a step toward a new drug delivery system that could find its way into cancer therapy, creating the equivalent of a mine floating through the blood waiting to delivery its lethal package to tumor cells when triggered remotely.

A team, led by Sangeeta Bhatia, M.D., Ph.D., an associate professor in the Harvard-MIT Division of Health Sciences and Technology (HST), constructed a nanoparticle containing a few metallic molecules so they could measure their accumulation. The particles have an affinity for the proteins commonly found on cancer cells and were measuring how many were collecting around a tumor by magnetic resonance imaging (MRI), when graduate student Geoff von Maltzahn, asked the next question: "Can we talk back to them?" And they could, causing the nanoparticle to give off heat.

They tethered a compound known to kill cancer cells to the nanoparticle using a small strand of DNA. Strands of DNA are highly susceptible to breaking under heat, and the breakage can be controlled by the length and sequence of the strand, as well as the infrared wavelength to which they are exposed.

The technique uses radio waves in the 350 and 400 kilohertz range to trigger the release of the compound. Radio waves pass harmlessly through the body. But, when they struck the nanoparticles, heat was produced, and the tethers broke.

To test their technique, they inserted a tumor-like mass into a mouse, and then injected the nanoparticle "mines" into the mouse's blood stream. They successfully released the test compound from the tether, but had trouble controlling the number of particles that actually collected on the tumor-like mass. To be effective, a 'critical mass' of particles has to collect around the tumor.

Work remains in order to make the technique usable in a clinical setting for diagnosis and treatment, but the proof of principle has encouraged Bhatia. In a press release from MIT, Bhatia says "Our overall goal is to create multifunctional nanoparticles that home to a tumor, accumulate, and provide customizable remotely activated drug delivery right at the site of the disease."

Results of the research appeared in the online edition of the journal Advanced Materials on November 15. Co-authors on the paper are Austin M. Derfus, a graduate student at the University of California at San Diego; Todd Harris, an HST graduate student; Erkki Ruoslahti and Tasmia Duza of The Burnham Institute in La Jolla, CA; and Kenneth S. Vecchio of the University of San Diego.