Posted: November 8, 2007

(Nanowerk News) Magnetic nanoparticles heated by a remote magnetic
field have the potential to release multiple anticancer drugs on
demand at the site of a tumor, according to a study published in the
journal Advanced Materials. Moreover, say the investigators who
conducted this research, these same nanoparticles can do double duty
as tumor imaging agents.

Two investigators from the Alliance for Nanotechnology in Cancer-
Sangeeta Bhatia, Ph.D., Massachusetts Institute of Technology, and
Erkki Ruoslahti, M.D., Ph.D., Burnham Institute-led this research
effort, which has the ultimate goal of developing a targeted,
multifunctional nanoparticle capable of providing time-tailored drug
release into tumors. To create such a platform, the investigators
started with dextran-coated iron oxide nanoparticles similar to the
ones now under development as magnetic resonance imaging contrast
agents. When stimulated by an oscillating magnetic field, these
nanoparticles absorb energy and become warm, a property that the
researchers capitalized on to create triggered drug release.

To these particles the researchers added a short piece of DNA to act
as a tether for one or more anticancer drugs linked to pieces of DNA
complementary to the particle-bound tether. At body temperature, the
complementary strands of DNA form the famous double helix, creating a
stable link between drug molecule and nanoparticle. But when the
nanoparticle becomes warm as a result of an applied oscillating
magnetic field, the bonds holding the two strands of DNA together
become progressively weaker until the local temperature hits a
critical value, at which point the double helix unwinds and the drug
molecule diffuses away from the nanoparticle. The researchers also
showed that when they applied the magnetic field in pulses of 5
minutes duration every 40 minutes, drug release occured in bursts,
too.

Since this "melting temperature" depends on the length of the double
helix, the investigators reasoned that they could use tethers of
different lengths to produce one nanoparticle capable of releasing two
or more drugs in sequence. Indeed, when the researchers attached two
different model drug compounds to the nanoparticle using tethers of
two different lengths, they were able to trigger release of the drug
attached via the shorter tether and follow that with release of the
second drug, attached with the longer tether, by increasing the power
of the oscillating magnetic field.

This work, which was funded by the NCI's Alliance for Nanotechnology
in Cancer, is detailed in the paper "Remotely triggered release from
magnetic nanoparticles." Investigators from the University of
California, San Diego, also participated in this study. This paper was
published online in advance of print publication. An abstract of this
paper is not yet available.

Source: National Cancer Institute

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