Nanozyme Breakthrough Offers Hope Against Thrombosis And Stroke
This innovation targets abnormal platelet activation caused by oxidative stress, a key factor in conditions like pulmonary thromboembolism and ischemic stroke.
By Anubha Jain
Published : June 11, 2025 at 8:26 PM IST
Bengaluru: Researchers at the Indian Institute of Science (IISc) have developed a novel artificial nanozyme made from vanadium pentoxide that mimics natural antioxidant enzymes to regulate blood clotting. This innovation targets abnormal platelet activation caused by oxidative stress, a key factor in conditions like pulmonary thromboembolism and ischemic stroke. By safely controlling Reactive Oxygen Species (ROS), the nanozyme offers a promising alternative to conventional antiplatelet therapies.
Researchers led by G Mugesh, Professor at the Department of Inorganic and Physical Chemistry, IISc, have developed artificial metal-based 'nanozymes,' which scavenge reactive oxidative molecules. These nanozymes can potentially be used to clamp down on abnormal blood clotting caused by conditions like pulmonary thromboembolism — a disorder characterised by blood clot formation due to the overactivation of platelets.
Platelets are small, disc-shaped cells that circulate in the bloodstream and are naturally activated to aid in blood clotting, a normal physiological process. 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, blocking the vessels, disrupting blood flow, and contributing to thrombosis, a major cause of morbidity and mortality.
In this study, researchers developed spherical-shaped vanadium pentoxide (V₂O₅) nanozymes, which mimic the function of glutathione peroxidase, a key natural antioxidant enzyme. These nanozymes effectively reduce oxidative stress in platelets by controlling ROS levels, thereby regulating platelet activation and aggregation.
A key factor contributing to this overactivation is the presence of reactive oxygen species (ROS). These are highly reactive molecules formed as byproducts of oxygen metabolism in the human body. Under normal conditions, ROS levels are tightly regulated. However, when ROS accumulate beyond normal levels, they can trigger platelet activation and aggregation, contributing to clot formation.
The body's natural antioxidant enzymes help maintain ROS balance, but under high oxidative stress, these enzymes become insufficient. This calls for synthetic alternatives that can mimic the function of natural enzymes — known as nanozymes. These are nanomaterials designed to imitate the activity of antioxidant enzymes and help regulate ROS levels.
Professor G Mugesh talked in detail about the entire process and the research study.
Importance of Redox Chemistry and Metal Oxidation State
Prof. Mugesh said that the mechanism behind these nanozymes relies on oxidation-reduction (redox) reactions, which are chemical processes where electrons are transferred. The team synthesised redox-active nanomaterials. Metals like vanadium, which can exist in multiple oxidation states, play a crucial role. In this case, the +5 oxidation state of vanadium is essential for the nanozyme’s activity, where the +4 oxidation state is toxic to the cells. Maintaining this oxidation state is critical for the nanomaterial to effectively mimic enzymatic function.
Applications in Ischemic Stroke
In addition to pulmonary thromboembolism, the team is exploring the use of these nanozymes for treating ischemic stroke — a serious condition in which a clot blocks blood flow to the brain, potentially leading to neuron damage and neurodegeneration. Prof. Mugesh stressed that by controlling platelet activity and preventing excessive clotting, these nanozymes could serve as a therapeutic tool in such stroke-related events.
Biocompatibility and Material Design
Talking about vanadium pentoxide as the core material for the nanozyme, Prof. Mugesh said that the choice of material is crucial. Vanadium, a trace element present in the human body, is considered biocompatible, making it suitable for biomedical applications. In contrast, heavy metals like arsenic or cadmium are highly toxic and unsuitable for use in living systems.
Discussing the shape and oxidation state of the nanozyme, which influence its ability to mimic glutathione peroxidase, the Professor said that nanomaterials have different morphologies, shapes, and sizes and influence their functionality. If the particles are too large, they cannot enter platelets, and their therapeutic effects cannot be realised. Morphology is how nanomaterials look under the microscope, as these are tiny materials that can’t be seen with the naked eye. Researchers found that spherical nanostructures of V₂O₅ exhibit superior activity compared to other morphologies (e.g., rods, wires, or flower-like shapes), likely due to better surface area and optimal size for cellular interaction.
Controlling ROS Without Disrupting Normal Physiology
While emphasising that the nanozyme selectively targets only excessive platelet activation without disturbing normal haemostasis, Prof. Mugesh said that elevated ROS levels are harmful, a baseline level of ROS is necessary for normal cell function. Therefore, the nanozymes must strike a balance — scavenging excess ROS without completely eliminating it. Importantly, the team confirmed that the nanozymes do not interfere with normal physiological blood clotting, unlike conventional antiplatelet drugs, which can cause excessive bleeding by disrupting the body's ability to form clots during injury.
Synthesis and Safety Assessment
When asked the challenges the team faced in synthesising the nanozyme with a stable +5 oxidation state, Prof. Mugesh replied that synthesising these nanozymes involved carefully controlled chemical reactions, with parameters such as temperature and pH finely tuned by using different characterisation and chemical methods. They then isolated platelets from human blood, activated them using physiological agonists, and tested how effectively the different nanozymes could prevent excess platelet aggregation.
Before conducting animal trials, the researchers ensured the purity of the nanomaterial to avoid introducing toxicity. Prof. Mugesh elaborated that during the experiments, animals were monitored over five days, and their organs, especially the lungs, which are primarily affected in pulmonary thromboembolism, were examined post-mortem to assess safety and efficacy.
The team 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.
Toward Clinical Applications
When asked how the nanozyme compares to conventional antiplatelet or anticoagulant drugs in terms of its mechanism and safety profile, Prof. Mugesh explained that current antiplatelet therapies are often associated with significant side effects, such as uncontrolled bleeding. In contrast, this nanozyme-based approach does not extend bleeding time, offering a promising alternative. While mouse models share many pathways with human platelet biology, further studies are necessary to evaluate the performance of these nanozymes in human systems.
Scaling this research towards clinical trials in humans, the Professor said that although many of the pathways involved in platelet activation and aggregation are shared between mice and humans, nanozymes may interact differently in human systems. This presents an additional challenge for scientists, who must carefully evaluate and validate the safety and efficacy of nanozymes in the human body before advancing to clinical applications.
When asked how such therapies could be made affordable and accessible if proven effective, the professor explained that the materials used for synthesising the nanozymes are inexpensive and readily available, and the synthesis process is simple and scalable. This means that, if successful in clinical trials, the therapy could be produced in bulk at low cost, making it widely accessible for patients.
This breakthrough represents a significant stride in nanomedicine, offering a safer and more precise method to combat life-threatening clotting conditions.
