Novel nanozyme prevents excess clotting

Researchers at the Indian Institute of Science (IISc) have developed an artificial metal-based nanozyme that can potentially be used to clamp down on abnormal blood clotting caused by conditions like pulmonary thromboembolism (PTE).

The work is published in the journal Angewandte Chemie International Edition.

Under normal circumstances, when a blood vessel is injured, specialized blood cells called platelets get activated and cluster together around the vessel to form protective blood clots. This process, known as the blood clotting cascade (hemostasis), involves a complex series of protein interactions triggered by signals from physiological agonists (chemicals) such as collagen and thrombin.

However, when these signals go haywire in conditions like PTE or diseases like COVID-19, oxidative stress and levels of toxic reactive oxygen species (ROS) increase, leading to over-activation of platelets. This triggers the formation of excess clots in the blood vessel, contributing to thrombosis, a major cause of morbidity and mortality.

To tackle this challenge, researchers led by G Mugesh, professor at the Department of Inorganic and Physical Chemistry, have developed nanomaterials that mimic the activity of natural antioxidant enzymes, which scavenge reactive oxidative molecules.

These “nanozymes” work by controlling ROS levels, thereby preventing the over-activation of platelets that leads to excess clot formation or thrombosis.

The team synthesized redox active nanomaterials of different sizes, shapes, and morphologies via a series of controlled chemical reactions starting from small building blocks. They then isolated platelets from human blood, activated them using physiological agonists, and tested how effectively the different nanozymes could prevent excess platelet aggregation.

The team found that spherical-shaped vanadium pentoxide (V₂O₅) nanozymes were the most efficient—these materials mimic a natural antioxidant enzyme called glutathione peroxidase to reduce oxidative stress.

“It was challenging to get the pure form of the nanozyme with only the +5 oxidation state of vanadium oxide. This was important because the +4 oxidation state is toxic to the cells,” explains Sherin GR, Ph.D. student and one of the lead authors.

“The unique chemistry of the vanadium metal is crucial because the redox reactions that reduce ROS levels are happening on the surface of the vanadium nanomaterial,” adds Mugesh.

The team injected the nanozyme in a mouse model of PTE and found that it significantly reduced thrombosis and increased the animals’ survival rates. They also observed the weight, behavior, and blood parameters of the animal for up to five days after injecting the nanozyme, and did not find any toxic effects.

Anti-platelet drugs that target thrombosis sometimes have side effects such as increased bleeding.

“Unlike conventional anti-platelet drugs that interfere with physiological hemostasis, the nanozymes modulate the redox signaling and do not interfere with normal blood clotting. This means that they won’t cause bleeding complications that are a major concern with current therapies,” says Bidare N SharathBabu, Ph.D. student and one of the lead authors.

The team now plans to explore the efficacy of the nanozyme in preventing ischemic stroke, which is also caused by clogging of blood vessels. “We are hopeful about clinical studies in humans because we have done our experiments with human platelets and they worked,” says Mugesh.