BENGALURU: A team of researchers from the Indian Institute of Science (IISc), Bengaluru, have developed a new method which will help control abnormal blood clotting conditions, including Pulmonary Thromboembolism (PTE).
The team from Department of Inorganic and Physical Chemistry have developed an artificial metal-based nanosyme that mimics the activity of natural antioxidant enzymes which help in clotting blood.
The research paper — Vanadia Nanozymes Inhibit Platelet Aggregation, Modulate Signaling Pathways and Prevent Pulmonary Embolism in Mice — published on May 11 was made public on Tuesday.
It explained that 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 is known as blood clotting cascade (haemostasis). But when this does not happen in conditions like PTE or diseases like Covid-19, the oxidative stress and levels of toxic Reactive Oxygen Species (ROS) increases, 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.
The nanomaterials developed by the researchers mimic the activity of natural antioxidant enzymes and they control the ROS levels, thereby preventing the over-activation of platelets that leads to excess clot formation or thrombosis, the report stated.
The team synthesised redox active nanomaterials of different sizes, shapes and morphologies through 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 researchers explained in the report.
Sherin GR, PhD student and co-author of the paper said, they found spherical-shaped vanadium pentoxide nanozymes were the most efficient. These material 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,” added G Mugesh, Professor, and co-author of the paper.
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, behaviour, and blood parameters of the animal for up to five days after injecting the nanozyme, and did not find any toxic effects, the report added.
Anti-platelet drugs that target thrombosis sometimes have side effects such as increased bleeding. “Unlike conventional anti-platelet drugs that interfere with physiological haemostasis, the nanozymes modulate the redox signalling 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,” said Bidare N Sharath Babu, PhD student and another co-author.