Many natural and synthetic antioxidants help defend the body against oxidative stress—a biochemical imbalance that can damage cells and lead to illnesses such as diabetes, Alzheimer’s and cancer. However, these materials can become unstable and less effective over time.

A new polymer developed by a team of researchers from the Department of Energy’s (DOE’s) Oak Ridge National Laboratory (ORNL) and the University of Alabama at Birmingham (UAB) may overcome these problems. The polymer, known as manganoporphyrin, can continually inhibit oxidants without breaking down.

The researchers combined their synthetic antioxidant with tannic acid, a natural antioxidant, to create a versatile material that could potentially improve drug delivery methods and other biomedical applications. Using neutrons at ORNL’s High Flux Isotope Reactor (HFIR), they studied the complementary properties of the combination and published their findings in Chemistry of Materials.

“This synergistic relationship produced a superior antioxidant,” said UAB researcher Veronika Kozlovskaya. “The polymer cannot work without the tannic acid, but the tannic acid is not as efficient alone.”

The team used nondestructive neutron scattering at the Bio-SANS instrument, HFIR beamline CG-3, to compare the antioxidant activity of hollow microcapsules made with and without manganoporphyrin.

By measuring the thickness of the capsules’ outer shells before and after exposing them to oxidants, they observed that the samples containing manganoporphyrin were stronger and more efficient. These antioxidant capsules successfully retaliated against the oxidant onslaught while hardly degrading, whereas the capsules without the crucial polymer progressively became much thinner and weaker.

“Neutron scattering was the only method capable of measuring these soft, nanometer-thin shells to determine their chemical stability in the presence of oxidants,” said UAB associate professor Eugenia Kharlampieva. “Because of its catalytic abilities, the new material provided more stability against the threat of oxidative stress.”

Fundamental research on this material could eventually provide a safer alternative to immunosuppressive drugs, which treat autoimmune diseases and prevent the rejection of medical implants or transplanted organs by weakening the immune system. Left alone, the immune system would identify any foreign objects as hostile invaders to eliminate.

Although immunosuppressive drugs prevent this reaction, they also make patients more susceptible to infections, viruses, and other harmful pathogens the immune system would normally dispel. For people whose immune systems are compromised by diseases such as diabetes or arthritis, further exhausting the body’s defenses can be especially dangerous.

In theory, a thin coating of the new antioxidant could be used to simply shield transplanted cell tissues or medical implants from view. Similarly, encapsulating medications inside the material would allow the drugs to dampen autoimmune processes without severely weakening the immune system.

“The material itself can modify immune responses, and this additional benefit means you can coat any foreign object and make it invisible to the immune system for the duration of that person’s lifetime,” Kharlampieva said.

The manganoporphyrin–tannic acid material may also have the ability to focus treatments on affected areas without damaging surrounding healthy tissue. For example, chemotherapy creates side effects throughout the body, regardless of where the cancer is located, and a more targeted approach would help reduce these complications.

“Because manganoporphyrin is permanently tethered to the capsule material, it is possible to localize the antioxidant activity to the vicinity of the microcapsules,” said Bio-SANS instrument scientist Volker Urban. “If we find a way to confine chemotherapy chemicals to tumor sites, that would be a significant breakthrough.”

The team is planning future studies to identify specific applications for this potent polymer, which Kharlampieva hopes will be extensive.

“Our ongoing goal is to help improve any biomedical field of study that requires suppression of immune responses,” she said.

The research is supported by the National Science Foundation’s Division of Materials Research grant 1608728. HFIR is a DOE Office of Science User Facility. UT-Battelle manages ORNL for the DOE Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, please visit—by Elizabeth Rosenthal