Inflammation
is the hallmark of many human diseases, from infection to
neurodegeneration. The chemical balance within a tissue is disturbed,
resulting in the accumulation of reactive oxygen species (ROS) such as
hydrogen peroxide, which can cause oxidative stress and associated toxic
effects.
Although
some ROS are important in cell signaling and the body’s defense
mechanisms, these chemicals also contribute to and are indicators of
many diseases, including cardiovascular dysfunction. A non-invasive way
of detecting measurable, low levels of hydrogen peroxide and other ROS
would provide a viable way to detect inflammation. Such a method would
also provide a way to selectively deliver drugs to their targets.
Adah
Almutairi, PhD, associate professor at the Skaggs School of Pharmacy
and Pharmaceutical Sciences, the Department of NanoEngineering, and the
Materials Science and Engineering Program at the University of
California, San Diego, and colleagues have developed the first
degradable polymer that is extremely sensitive to low but biologically
relevant concentrations of hydrogen peroxide.
Their work is currently published in the online issue of the Journal of the American Chemical Society.
These
polymeric capsules, or nanoparticles, are taken up by macrophages and
neutrophils—immune system cells that rush to the site of inflammation.
The nanoparticles then release their contents when they degrade in the
presence of hydrogen peroxide produced by these cells.
“This
is the first example of a biocompatible way to respond to oxidative
stress and inflammation,” said Almutairi, director of the UC San Diego
Laboratory of Bioresponsive Materials. “Because the capsules are
tailored to biodegrade and release their cargo when encountering
hydrogen peroxide, they may allow for targeted drug delivery to diseased
tissue.”
Almutairi
is looking to test this method in a model of atherosclerosis.
“Cardiologists have long needed a non-invasive method to determine which
patients are vulnerable to a heart attack caused by ruptured plaque in
the arteries before the attack,” she said. “Since the most dangerous of
plaques is inflamed, our system could provide a safe way to detect and
treat this disease.”
Additional
contributors to the study include Caroline de Gracia Lux, Shivanjali
Joshi-Barr, Trung Nguyen, Enas Mahmoud, Eric Schopf and Nadezda Fomina.
This
research was supported by the NIH Director’s New Innovator Award
(1DP2OD006499-01) and a King Abdulaziz City for Science and Technology
center grant to the Center of Excellence in Nanomedicine at UC San
Diego.
Source: University of California, San Diego
