Indian Institute of Science, Bengaluru
| Photo Credit: File photo

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).

According to IISc., under normal circumstances, when a blood vessel is injured, specialised 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 (haemostasis), 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 in 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 synthesised 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.

“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,” said Prof. Mugesh.

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

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,” said Prof. Mugesh.