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Eva Harth in her laboratory.
Photo �
Neil Brake |
Harth, who is an assistant professor of
chemistry at Vanderbilt University, has created a �nanosponge�
specially designed to carry large numbers of drug molecules. She has
also discovered a �molecular transporter� that, when attached to the
nanosponge, carries it and its cargo across biological barriers into
specific intracellular compartments, which are very difficult places
for most drugs to reach. She has shown that her system can reach
another difficult target: the brain. Experiments have shown that it
can pass through the brain-blood barrier. In addition, she has:
successfully attached a special �targeting unit� that delivers drugs
to the surface of tumors in the lungs, brain and spinal cord and even
developed a �light kit� for her delivery system � fluorescent tags
that researchers can use to monitor where it goes.
Harth has taken a different approach from other
researchers working on nanotechnology for drug development. Instead of
trying to encapsulate drugs in nanoscale containers, she decided to
create a nanoparticle that had a large number of surface sites where
drug molecules could be attached. To do so, she adopted a method that
uses extensive internal cross-linking to scrunch a long, linear
molecule into a sphere about 10 nanometers in diameter, about the size
of a protein. Nanoparticles like this are called nanosponges.
�We can really load this up with a large number of
drug molecules,� she says.
Working with Heidi Hamm, the Earl W. Sutherland Jr.
Professor of Pharmacology at Vanderbilt, Harth synthesized a dendritic
molecule with the ability to slip through cell membranes and reach the
cell nucleus. They figured out how to attach this �transporter� to her
nanoparticle and showed that the transporter can pull the nanoparticle
after it into cellular compartments. They also demonstrated that the
transporter can deliver large molecules � specifically peptides and
proteins � into specific sub-cellular locations.
�Peptides and proteins can act as drugs, just like
smaller molecules,� Harth says. �However, there is not much activity
in this area because people haven�t had a method for getting them into
cells. Now that there is a way to do it, but that may change.�
Hamm studies G proteins, arguably the most
important signaling molecules in the cell. Scientists think that many
diseases, including diabetes and certain forms of pituitary cancer,
are caused by malfunctioning G proteins. She and Harth are
collaborating on using the transporter to deliver peptides produced by
G proteins that disrupt signaling pathways.
�Eva�s methods for drug delivery are very novel and
versatile and can be adapted to delivery of proteins, peptides, DNA
and smaller chemical compounds like most drugs. The breadth of
applications makes her technology very powerful,� Hamm says.
The chemist is also collaborating with Dennis E.
Hallahan, professor of radiation oncology at Vanderbilt, to apply the
drug delivery system to fighting cancer. Hallahan�s lab had identified
a molecule that targets a surface feature on lung carcinomas. Harth took the molecule, improved it, attached it to her nanoparticle and
the two of them determined that the combination is capable of
delivering drugs to the surface of lung tumors.
She is now working with Hallahan to adapt her
delivery system to carry cisplatinum, a traditional chemotherapy agent
that is used to treat a number of different kinds of cancer but is
highly toxic and has a number of unpleasant side effects.
By delivering the anti-cancer agent directly to the
cancerous tissues, Eva�s system decreases the adverse effects on other
tissues and increases its potency by delivering a higher concentration
of the drug directly on the cancer, Hallahan explains.
�The people in my lab have tried at a number of
different drug delivery systems and Eva�s works the best of those
we�ve looked at,� Hallahan says.
Vanderbilt is applying for two patents on the
system. |
