[Editors] MIT develops nanoparticles to battle cancer

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

======================================
MIT develops nanoparticles to battle cancer
======================================

For Immediate Release
WEDNESDAY, JAN. 31, 2007
Contact: Elizabeth A. Thomson, MIT News Office
Phone: 617-258-5402
Email: thomson at mit.edu

CAMBRIDGE, Mass.--On a quest to modernize cancer treatment and 
diagnosis, an MIT professor and her colleagues have created new 
nanoparticles that mimic blood platelets. The team wants to use these 
new multifunctional particles to carry out different medical missions 
inside the body, from imaging to drug delivery.

After years of research, "we still treat cancer with surgery, 
radiation and chemotherapy," said Sangeeta Bhatia, an associate 
professor in MIT's Department of Electrical Engineering and Computer 
Science and the Harvard-MIT Division of Health Sciences and 
Technology. "People are now starting to think more in terms of 
'Fantastic Voyage,' that sci-fi movie where they miniaturized a 
surgical team and injected it into someone."

The National Cancer Institute has recognized the value of Bhatia's 
work and has awarded her a grant to continue this line of research. 
Bhatia and collaborators Michael J. Sailor, chemist and materials 
scientist at the University of California at San Diego, and Erkki 
Ruoslahti, tumor biologist at the Burnham Institute for Medical 
Research, will receive $4.3 million in funding over five years.

The grant will allow the team to continue work on promising 
nanoparticle solutions that, while not quite miniature surgical 
teams, do have the potential to help identify tumors and deliver 
chemotherapy locally.

One solution already under way involves using nanoparticles for 
cancer imaging. By slipping through tiny gaps that exist in 
fast-growing tumor blood vessels and then sticking together, the 
particles create masses with enough of a magnetic signal to be 
detectable by a magnetic resonance imaging (MRI) machine. "This might 
allow for noninvasive imaging of fast-growing cancer 'hot spots' in 
tumors," said Bhatia. The team will continue this research by testing 
the imaging capabilities in animal models.

Another solution, described in the Jan. 16 issue of the Proceedings 
of the National Academy of Sciences, is a novel "homing" nanoparticle 
that mimics blood platelets. Platelets flow freely in the blood and 
act only when needed, by keying in on injured blood vessels and 
accumulating there to form clots. Similarly, these new nanoparticles 
key in on a unique feature of tumor blood vessels.

Ruoslahti had identified that the lining of tumor vessels contains a 
meshwork of clotted plasma proteins not found in other tissues. He 
also identified a peptide that binds to this meshwork. By attaching 
this peptide to nanoparticles, the team created a particle that 
targets tumors but not other tissues. When injected into the 
bloodstream of mice with tumors, the peptide sticks to the tumor's 
clotted mesh.

An unexpected feature of the nanoparticles is that they clump 
together and, in turn, induce more clumping. This helps to amplify 
the effects of the particles. "One downside of nanotechnology is that 
you shrink everything, including the cargo," said Bhatia. "You need 
particles to accumulate for them to be effective."

The assembly of these new particles concentrates them in a way that 
may improve on the tumor imaging capabilities the team described 
earlier. These particles also have the potential to be used as a 
means to cause clots big enough to choke off the blood supply to the 
tumor or to deliver drugs directly into the tumor.

But there are challenges ahead. For one, the team must verify that 
these particles only accumulate where they are desired. Also, they 
need better ways to keep the nanoparticles in the bloodstream. The 
body naturally clears these foreign bodies through the liver and 
spleen.

The team devised a means to temporarily disable this natural clearing 
system. They created a "decoy" particle that saturates this clearing 
system temporarily, allowing the active nanoparticles time to 
accumulate in the tumor tissue. These decoys, however, were toxic to 
some mice and also disable a system that normally protects the body, 
leaving it vulnerable to other invaders.

This challenge dovetails nicely with Bhatia's other work. Not only 
does she have expertise in liver functions, she directs the facility 
at the MIT Center for Cancer and Nanotechnology Excellence that 
analyzes new materials for toxicity and is working to standardize the 
guidelines for nanomaterial toxicity.

"We need to be able to understand the whole system better to be able 
to move the field forward," she said.

In addition to Sailor and Ruoslahti, Bhatia's co-authors on the 
recent PNAS paper are Dmitri Simberg, Tasmia Duza, Markus Essler, Jan 
Pilch, Lianglin Zhang and Austin M. Derfus, all from lead author 
Ruoslahti's laboratories at the University of California at Santa 
Barbara; Robert M. Hoffman, Ji Ho Park and Austin M. Derfus of the 
University of California at San Diego; and Meng Yang and Robert M. 
Hoffman of AntiCancer Inc.

The research was supported by grants from the National Cancer 
Institute and from the National Institutes of Health.

--END--

Written by Elizabeth Dougherty
Harvard-MIT Division of Health Sciences and Technology