W. Andy Tao’s nanopolymers can better assess whether cancer drugs are reaching their targets, a development that may reduce the side effects of those drugs. Credit: Purdue Agricultural Communication photo/Tom Campbell
Univ. biochemist has
demonstrated a process using nanotechnology to better assess whether cancer
drugs hit their targets, which may help reduce drug side effects.
W. Andy Tao, an associate professor of biochemistry
analytical chemistry, developed a nanopolymer that can be coated with drugs,
enter cells, and then be removed to determine which proteins in the cells the
drug has entered. Since they’re water-soluble, Tao believes the nanopolymers
also may be a better delivery system for drugs that do not dissolve in water
“Many cancer drugs are not very specific. They target
many different proteins,” said Tao, whose findings were published in Agnewandte Chemie International Edition.
“That can have a consequence—what we call side effects.”
In addition to the drug, the synthetic nanopolymer is
equipped with a chemical group that is reactive to small beads. The beads
retrieve the nanopolymer and any attached proteins after the drug has done its
work. Tao uses mass spectrometry to determine which proteins are present and
have been targeted by the drug.
Knowing which proteins are targeted would allow drug
developers to test whether new drugs target only desired proteins or others as
well. Eliminating unintended protein targets could reduce the often-serious
side effects associated with cancer drugs.
Tao said there currently is no reliable way to test drugs
for off-targeting. He said drugs are often designed to inhibit or activate the
function of a biomolecule associated with cancer, but those drugs tend to fail
in late-stage clinical tests.
Tao also believes his nanopolymers could better deliver
drugs to their targets. Since they are nanosized and water soluble, the
nanopolymers could gain access to cells more effectively than a standalone drug
that is only minimally water-soluble.
Tao demonstrated the nanopolymer’s abilities using human
cancer cells and the cancer drug methotrexate. The nanopolymers were tracked
using a fluorescent dye to show they were entering cells. Then, Tao broke the
cells and retrieved the nanopolymers.
Tao has shown the nanopolymer’s ability using a metabolic
drug, which are small, low-cost drugs, but are less target specific and have
more side-effects. He now plans to do the same using drugs that are based on
synthetic peptides, which are larger and more expensive but more specific and
with fewer side effects.
The National Institutes of Health’s National Center
for Research Resources and a National Science Foundation Career Grant funded