Homework 02

Electric fields deliver drugs into tumors

A

Chemotherapy has been a mainstay of cancer treatment for decades. But most of these drugs are
toxic to healthy cells, and others have a hard time penetrating tumors. Now researchers report that
theyve come up with a potential solution for both problems. They used electric fields to drive chemo
compounds specifically into difficult-to-treat tumors in animals, dramatically increasing the drugs
concentration within the tumor and shrinking it.
Like all potential cancer treatments from animal studies, the approach has a long way to go before it
reaches patients. However, the strategy is encouraging, says Robert Langer, a chemical engineer at the
Massachusetts Institute of Technology in Cambridge and an expert in drug delivery, who wasnt
involved with the work. The initial data look quite promising.
Joseph DeSimone, a chemist at the University of North Carolina, Chapel Hill, who headed up the
new study, says he became interested in working on hard-to-treat tumors after years of developing
novel approaches to deliver drugs orally. He also recently lost a close colleague to pancreatic cancer,
who like other patients with the disease was ravaged by the side effects of chemo.
DeSimone was familiar with a different approach for delivering chemo drugs locally into tumors that
involves putting them in biodegradable polymers that slowly decay after being implanted next to a
tumor, releasing a steady supply of the drug. But that approach hasnt worked well with pancreatic
cancer. Like some other tumors, pancreatic tumors build up a high internal fluid pressure, which pushes
against medicines trying to diffuse in and prevents them from concentrating deep within the cancerous
tissue.
In the last few years, other research groups had shown that it was possible to use small electric fields
to drive medicines into the eye and bladder. DeSimone and his colleagues wanted to see if they could
use the same strategy to drive chemotherapeutic drugs into solid tumors. To do so, they built a setup
with a small reservoir designed to hold a liquid chemotherapy drug. This reservoir also contained one
of two electrodes that create the electric field needed to drive the drug into nearby tumor tissue. In one
setup, which was designed to deliver chemotherapy drugs to tumors deep within the body, the
researchers implanted the reservoir and its electrode on one side of a tumor, while they implanted the
counterelectrode on the tumors opposite side. In the other setup, which was designed to treat tumors
just under the skin, the reservoir containing one electrode was placed on the skin just above the tumor
in mice, while the second electrode was placed on the skin on the opposite side of the animals body.
So in the latter case, the electric field generated between the two electrodes pushed the drugs through
the skin into the tumor below.
DeSimone and colleagues tested their drug delivery method on mice with pancreatic or breast
cancer. They also implanted their devices on the surface of the pancreas of dogs without tumors, in an
effort to better gauge the flow of drugs into tissues of larger animals such as humans. In all the studies,
the devices required low electric currents and voltages, below the pain register in the animals, to drive
the drugs into the tumors. The approach works, DeSimone explains, because many liquid drug
molecules are polar, which causes them to move in an electric field toward an electrode with an
opposite charge from the nearby electrode where they start.
The team got several promising results. In one experiment, the researchers started with mice that had
been implanted with human pancreatic cancer tumors. One group of mice was then implanted with the
electrode setup and administered an anticancer drug called gemcitabine twice a week for 7 weeks.
Control animals received either saline through the same electrode setup or intravenous (IV) doses of
saline or gemcitabine. The researchers report online today in Science Translational Medicine that the
animals in the experimental group had far higher gemcitabine concentrations in their tumors compared
with mice that received the IV drug. That caused the tumors to shrink dramatically in the experimental
animals, whereas tumors in mice that received IV gemcitabine or saline continued to grow.
http://news.sciencemag.org/chemistry/2015/02/electric-fields-deliver-drugs-tumors
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