[Editors] MIT: Remote-control nanoparticles deliver drugs directly into tumors

[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

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MIT: Remote-control nanoparticles deliver drugs directly into tumors
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For Immediate Release
FRIDAY, NOV. 16, 2007
Contact: Elizabeth A. Thomson, MIT News Office -- Phone: 617-258-5402  
-- Email: thomson at mit.edu

PHOTO, GRAPHIC AVAILABLE

CAMBRIDGE, MA--MIT scientists have devised remotely controlled  
nanoparticles that, when pulsed with an electromagnetic field,  
release drugs to attack tumors. The innovation, reported in the Nov.  
15 online issue of Advanced Materials, could lead to the improved  
diagnosis and targeted treatment of cancer.

In earlier work the team, led by Sangeeta Bhatia, M.D.,Ph.D., an  
associate professor in the Harvard-MIT Division of Health Sciences &  
Technology (HST) and in MIT's Department of Electrical Engineering  
and Computer Science, developed injectable multi-functional  
nanoparticles designed to flow through the bloodstream, home to  
tumors and clump together. Clumped particles help clinicians  
visualize tumors through magnetic resonance imaging (MRI).

With the ability to see the clumped particles, Bhatia's co-author in  
the current work, Geoff von Maltzahn, asked the next question: “Can  
we talk back to them?”

The answer is yes, the team found. The system that makes it possible  
consists of tiny particles (billionths of a meter in size) that are  
superparamagnetic, a property that causes them to give off heat when  
they are exposed to a magnetic field. Tethered to these particles are  
active molecules, such as therapeutic drugs.

Exposing the particles to a low-frequency electromagnetic field  
causes the particles to radiate heat that, in turn, melts the tethers  
and releases the drugs. The waves in this magnetic field have  
frequencies between 350 and 400 kilohertz-the same range as radio  
waves. These waves pass harmlessly through the body and heat only the  
nanoparticles. For comparison, microwaves, which will cook tissue,  
have frequencies measured in gigahertz, or about a million times more  
powerful.

The tethers in the system consist of strands of DNA, “a classical  
heat sensitive material,” said von Maltzahn, a graduate student in  
HST. Two strands of DNA link together through hydrogen bonds that  
break when heated. In the presence of the magnetic field, heat  
generated by the nanoparticles breaks these, leaving one strand  
attached to the particle and allowing the other to float away with  
its cargo.

One advantage of a DNA tether is that its melting point is tunable.  
Longer strands and differently coded strands require different  
amounts of heat to break. This heat-sensitive tuneability makes it  
possible for a single particle to simultaneously carry many different  
types of cargo, each of which can be released at different times or  
in various combinations by applying different frequencies or  
durations of electromagnetic pulses.

To test the particles, the researchers implanted mice with a tumor- 
like gel saturated with nanoparticles. They placed the implanted  
mouse into the well of a cup-shaped electrical coil and activated the  
magnetic pulse. The results confirm that without the pulse, the  
tethers remain unbroken. With the pulse, the tethers break and  
release the drugs into the surrounding tissue.

The experiment is a proof of principal demonstrating a safe and  
effective means of tunable remote activation. However, work remains  
to be done before such therapies become viable in the clinic.

To heat the region, for example, a critical mass of injected  
particles must clump together inside the tumor. The team is still  
working to make intravenously injected particles clump effectively  
enough to achieve this critical mass.

“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,” said Bhatia.

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.

The research was supported by grants from the David and Lucile  
Packard Foundation, the National Cancer Institute of the National  
Institutes of Health. Dervis was supported by a G.R.E.A.T fellowship  
from the University of California Biotechnology Research and  
Educational Program.

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