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.
Posted 19th November 2007
