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Monocytes -- a kind of white blood cell -- carry drug-loaded backpacks (red). (The scale bar is 5 micrometers.) Credit: Roberta Polak & Rosanna Lim
Drug therapies for many conditions end up treating
the whole body even when only one part—a joint, the brain, a wound—needs it.
But this generalized approach can hurt healthy cells, causing nasty side
effects. To send drugs to specific disease locations and avoid unwanted
symptoms, researchers developed cellular "backpacks" that are
designed to carry a therapeutic cargo only to inflamed disease sites.
The
researchers present their work today at the 251st National Meeting &
Exposition of the American Chemical Society (ACS).
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"What
we want to do is take advantage of immune cells whose job it
is to seek out disease in the body, and use them to deliver cargo for us,"
says Roberta Polak, a postdoctoral research associate. "How do we do that?
Our lab developed cellular backpacks that can be loaded with therapeutic
compounds and unloaded."
Polak and
fellow researchers in the
Massachusetts Institute of Technology (MIT) labs of Michael Rubner, Ph.D., and
Robert Cohen, Ph.D., make the backpacks by stacking ultra-thin layers of polymer
materials on top of each other. According to Rubner, they could be used to
treat a wide range of diseases from cancer to Parkinson's.
The
resulting pack has different functional regions. One is Velcro-like, attaching
via antibody-antigen binding to immune cells, such as monocytes and
macrophages. These are the body's defense cells that travel to sites of
inflammation—a natural reaction to infection and disease—and gobble up foreign
invaders or attack cancer cells. In vitro testing has shown that the backpacks
can stick to the surfaces of the immune cells without getting engulfed. In
collaboration with the group of Samir Mitragotri at the University of
California at Santa Barbara, the MIT team has also demonstrated in mice that
these backpack-functionalized immune cells accumulate in locations where
inflammation—a sign of disease—occurs.
But there
was a problem. The medicine they were using to test the backpacks, a cancer drug called doxorubicin, was leaking
out—even during the initial fabrication process. So Polak worked on this part
of the backpack, its payload region. To stop the premature release of the drug,
she trapped it in liposomes, tiny bubbles that have already been used to carry
therapeutic compounds for other delivery systems, and then incorporated them
into the backpacks. She found that she could fit nine times the amount of
doxorubicin in the liposomes than in the backpacks alone, potentially
transforming them into an even more potent weapon.
To
control the release of the drug payload, Polak used liposomes that are
echogenic, or sensitive to ultrasound. So in principle, when backpacks infused
with these bubbles reach their destination, they can be burst open with
ultrasound waves.
Now, to
see how well they work to treat a specific disease, Polak is collaborating with
Elena Batrakova, Ph.D., at the University of North Carolina at Chapel Hill.
Batrakova has been working with mice to develop new treatments for brain
inflammation, a characteristic of diseases such as Parkinson's and Alzheimer's.
They want to see if they can use the backpacks to carry an
inflammation-fighting enzyme across the blood-brain barrier.
Explore further:
'Cellular
backpacks' attached to white blood cells that target inflammation can provide
therapy
More
information: Design
and Production of Functional Thin-Film Backpacks for Cell-Based Therapies, the
251st National Meeting & Exposition of the American Chemical Society (ACS),
2016.
http://phys.org/news/2016-03-cellular-backpacks-disease-minimizing-side.html
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