A team of researchers at the Indian Institute of Science (IISc) in Bengaluru has created a new metal-based nanozyme that may provide a safer solution to life-threatening blood clots without causing bleeding, which is a common side effect of current treatments. 

This development is especially relevant in the setting of pulmonary thromboembolism (PTE), a dangerous illness in which blood clots block arteries in the lungs, potentially leading to sudden death. According to the American Heart Association, venous thromboembolism, which includes PTE and deep vein thrombosis, affects about 10 million people worldwide each year and has a high mortality risk if not treated. 

Microscopic blood cells known as platelets normally form clots to halt bleeding when vessels break. However, in illnesses such as PTE or severe COVID-19, this process can become uncontrollable due to oxidative stress, which occurs when too many reactive oxygen species (ROS), or damaging chemicals, circulate in the bloodstream. These ROS overactivate platelets, causing deadly clots, a process known as thrombosis. 

Current treatments, such as blood thinners or antiplatelet pills, are used to prevent this, but they have dangerous side effects, including uncontrollable bleeding, because they interfere with the body's normal clotting function. 

To address this issue, an IISc team lead by Professor G. Mugesh from the Department of Inorganic and Physical Chemistry developed a family of artificial enzymes known as nanozymes. These mirror the body's endogenous antioxidants, which neutralise ROS and lessen oxidative stress. 

"We designed redox-active nanomaterials that can control ROS without affecting the normal clotting mechanism," says Prof. Mugesh. Redox reactions involve the exchange of electrons to neutralise harmful chemicals like ROS. 

Out of all the different types we looked at, a round nanozyme made from vanadium pentoxide (V₂O₅) turned out to be the best. This substance operates similarly to glutathione peroxidase, a potent natural antioxidant enzyme found in the human body. 

"It was difficult to isolate vanadium in its +5 oxidation state because the +4 form is toxic," explained Sherin GR, a PhD scholar and primary author. The team accomplished this using highly controlled chemical synthesis processes. 

After creating the nanozyme, researchers tested it on human blood platelets in a lab. When exposed to ROS and physiological agonists (natural compounds that cause clotting), the nanozyme effectively inhibited platelet activation. 

The nanozyme was then directly delivered into the bloodstream of a PTE mouse model. The findings were promising: thrombosis was greatly decreased, and survival rates increased. Importantly, the animals exhibited no symptoms of toxicity, such as changes in weight, attitude, or blood composition, even after five days. 

"This is a significant improvement over current antiplatelet drugs, which frequently cause bleeding," said Bidare N. Sharath Babu, another lead author. "Our nanozyme works by fine-tuning redox signals, rather than blocking the clotting cascade directly." 

The researchers now intend to investigate the nanozyme's efficacy in ischaemic stroke, another devastating illness caused by blood artery obstruction. Because its nanozyme works on human platelets in the lab, they are optimistic about clinical trials in the near future. 

If successful in humans, this research could pave the way for a novel approach to thrombosis treatment, avoiding the high-stakes trade-off between clot prevention and bleeding risk. 

"This approach doesn't stop clotting altogether — it just keeps it in check," according to Professor Mugesh. "That's what makes it so exciting from a health and safety perspective," he told me.