Sangeeta Bhatia - Working in harmony
MIT-designed nanoparticles communicate
with each other inside the body to target
tumors more efficiently.'
Anne Trafton, MIT News Office
June 20, 2011
For decades, researchers have been working to
develop nanoparticles that deliver cancer drugs
directly to tumors, minimizing the toxic side effects
of chemotherapy. However, even with the best of
these nanoparticles, only about 1 percent of the
drug typically reaches its intended target.
Now, a team of researchers from MIT, the Sanford-
Burnham Medical Research Institute and the
University of California at San Diego have designed
a new type of delivery system in which a first wave
of nanoparticles homes in on the tumor, then calls in
a much larger second wave that dispenses the
cancer drug. This communication between
nanoparticles, enabled by the body's own
biochemistry, boosted drug delivery to tumors by more than 40-fold in a mouse study.
This new strategy could enhance the effectiveness of many drugs for cancer and other diseases, says Geoffrey
von Maltzahn, a former MIT doctoral student now at Cambridge-based Flagship VentureLabs, and lead author of a
paper describing the system in the June 19 online edition of Nature Materials.
"What we've demonstrated is that nanoparticles can be engineered to do things like communicate with each other
in the body, and that these capabilities can improve the efficiency with which they find and treat diseases like
cancer," von Maltzahn says.
Senior author of the paper is Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and
Technology and Electrical Engineering and Computer Science and a member of MIT's David H. Koch Institute for
Integrative Cancer Research.
Von Maltzahn and Bhatia drew their inspiration from complex biological systems in which many components work
together to achieve a common goal. For example, the immune system works through highly orchestrated
cooperation between many different types of cells.
"There are beautiful examples throughout biology where at a system scale, complex behaviors emerge as a result
of interaction, cooperation and communication between simple individual components," von Maltzahn says.
Video: Nanoparticles that talk to one another
The MIT team's approach is based on the blood coagulation cascade — a series of reactions that starts when
the body detects injury to a blood vessel. Proteins in the blood known as clotting factors interact in a complex
chain of steps to form strands of fibrin, which help seal the injury site and prevent blood loss.
To harness the communication power of that cascade, the researchers needed two types of nanoparticles:
signaling and receiving.
Signaling particles, which make up the first wave, exit the bloodstream and arrive at the tumor site via tiny holes
in the leaky blood vessels that typically surround tumors (this is the same way that most targeted nanoparticles
reach their destination). Once at the tumor, this first wave of particles provokes the body into believing that an
injury has occurred at a tumor site, either by emitting heat or by binding to a protein that sets off the coagulation
Receiving particles are coated with proteins that bind to fibrin, which attracts them to the site of blood clotting.
Those second-wave particles also carry a drug payload, which they release once they reach the tumor.
In a study of mice, one system of communicating nanoparticles delivered 40 times more doxorubicin (a drug used
to treat many types of cancer) than non-communicating nanoparticles. The researchers also saw a
correspondingly amplified therapeutic effect on the tumors of mice treated with communicating nanoparticles.
To pave the path for potential clinical trials and regulatory approval, the MIT researchers are now exploring ways
to replace components of these cooperative nanosystems with drugs already being tested in patients. For
example, drugs that induce coagulation at tumor sites could replace the signaling particles tested in this study.
Jeffrey Brinker, professor of chemical engineering at the University of New Mexico, says the new strategy is a
clever way to improve drug delivery to tumor sites. "Instead of targeting the tumor itself, it's targeting a
microenvironment that they’ve created," he says. "By developing these nanosystems in a two-step approach, that
could be used in combination with a lot of other strategies."