International research team of the Moscow Institute of Steel and Alloys, Lomonosov Moscow State University and the University of North Carolina (Chapel Hill, USA) has developed a therapeutic complex based on multilayer polymer nanostructures of the antioxidant enzyme superoxide dismutase. The final product is a unique porous polymer capsule that is able to let free radicals pass inside it and neutralize them as a “reusable trap”. The new substance can be used for effective rehabilitation after acute injuries of the spinal cord, strokes and heart attacks, RIA Novosti reported. The results of the study are published in the Journal of Controlled Release.
Due to a hard blow (in case of a spinal injury), vessel rupture (in case of a stroke) or necrosis (infarction) the cessation of blood flow during arterial spasm or blockage in the organ’s nearest tissues leads to hypoxia, a pathological process associated with lack of oxygen. This factor blocks the end link of the respiratory chain in the cells and causes excess formation of so-called free radicals (active forms of oxygen). They, in turn, have a destructive effect on the cell membranes and trigger a chain of reactions leading to damage and death of cells and tissues. These complications provoke additional damage of the spinal cord and neuronal death, thus exacerbating the clinical condition.
An effective natural absorber of free radicals is a special antioxidant enzyme - superoxide dismutase (SOD1). Fast delivery of the substance to the damaged organ can alleviate oxidative stress against the background of excess free radicals and stop the process of tissue destruction. However, a significant problem is the instability of the enzyme in the bloodstream when administered intravenously to the patient: it quickly degrades, having not enough time to neutralize free radicals.
In order to create a stable therapeutic complex based on SOD1, we have developed catalytically active nanoforms of superoxide dismutase, the so-called “nanozymes”, - says Maxim Abakumov, head of the Biomedical Nanomaterials Laboratory at the Moscow Institute of Steel and Alloys, co-author of the development.
As a result, a porous polymer capsule (about 40-50 nanometers in size) with an enzyme molecule has been obtained. This capsule acts as a reusable trap, letting free radicals in and neutralizing them there.
"We have developed nanozymes with high enzymatic activity and the ability to preserve and protect SOD1 under physiological conditions that increase the circulation time of active SOD1 in the blood compared to free SOD1 molecules. The biological half-life of the substance was 60 vs. 6 minutes”, - Maxim Abakumov added.
Successful testing of the nanozymes model of SOD1 on rodents has proved the promise of the substance for removing free radicals, reducing inflammation and edema, as well as accelerating rehabilitation after spinal cord injury, stroke and heart attack. In the near future, the team plans to move on to preclinical trials.
Author: Vera Ivanova