A trap for radicals
Scientists have created a trap capsule for the treatment of stroke and spinal cord injury
Scientists from the international research team of the National Research Technological University "MISIS", 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 capable of passing free radicals inside and neutralizing them according to the principle of a "reusable trap". The new substance can be used for effective rehabilitation after acute spinal cord injuries, strokes and heart attacks. The results of the study are published in the Journal of Controlled Release (Nukolova et al., Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury).
From a blow (in case of spinal injury), rupture of a vessel (in case of stroke) or necrosis (heart attack), the cessation of blood flow with spasm of the arteries or their blockage in the nearest tissues of the organ leads to hypoxia – a pathological process associated with a lack of oxygen. This factor blocks the final link of the respiratory chain in cells and is the cause of excessive formation of so-called free radicals (reactive oxygen species). They, in turn, have a destructive effect on cell membranes and trigger a chain of reactions leading to damage and death of cells and tissues. These complications lead to additional damage to the spinal cord and death of neurons, aggravating the clinical picture.
An effective natural free radical scavenger is a special antioxidant enzyme - superoxide dismutase (SOD1). Prompt delivery of the substance to the damaged organ can mitigate oxidative stress against the background of an excess of free radicals and stop the process of tissue destruction. However, a significant problem is the instability of the enzyme in the bloodstream during intravenous administration to the patient: it is rapidly destroyed, without having time to carry out its work to neutralize free radicals.
"In order to create a stable therapeutic complex based on SOD1, we have developed catalytically active superoxide dismutase nanoforms, the so–called nanozymes," says Maxim Abakumov, one of the co-authors of the development, head of the Biomedical Nanomaterials laboratory at NUST MISIS. "In particular, we were the first in the world to receive a chemically "cross-linked" multilayer polyionic complex SOD1, where a surface coating of block copolymer and PEG-polyglutamic acid was additionally introduced for the first time."
As a result, a porous polymer capsule (approximately 40-50 nanometers in size) with an enzyme molecule was obtained. This capsule works as a reusable trap, letting in free radicals and neutralizing them there.
A drawing from an article in the Journal of Controlled Release – VM.
"We have developed nanozymes with high enzymatic activity and the ability to preserve and protect SOD1 under physiological conditions, which increase the circulation time of active SOD1 in the blood compared to free SOD1 molecules. The half–life of the substance was 60 versus 6 minutes," Maxim Abakumov added.
During the experimental tests of the substance, the research team led by Professor Alexander Kabanov of the University of North Carolina received encouraging laboratory results. A single intravenous injection of nanozymes containing 5000 conventional units of SOD1 per 1 kg of weight improved the recovery of motor functions in rats with moderate spinal cord injury. In addition, there was a decrease in swelling, compression of the spinal cord and the formation of post-traumatic cysts.
Thus, successful testing of the SOD1 enzyme nanozymes model on rodents 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 switch to preclinical trials.
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