Research Projects

Ischemic stroke remains a critical global health burden, ranking as the second leading cause of death and a major cause of long-term disability. In 2019 alone, it was responsible for 6.55 million deaths and 143 million disability adjusted life years. Ischemic stroke is mainly caused by arterial blockage that restricts blood flow to the brain, leading to neuronal damage. While platelet activation drives clot formation, current antiplatelet drugs pose bleeding risks during the acute phase. Additionally, the restoration of blood flow after ischemia leads to excessive production of reactive oxygen species, which accelerates oxidative damage in brain tissue. To counteract both thrombosis and oxidative stress, artificial enzyme like nanomaterials known as nanozymes have attracted significant attention due to their low cost, chemical stability, and adjustable catalytic activity. Among these, glutathione peroxidase mimicking nanozymes have shown strong therapeutic potential. Recent work demonstrated that vanadium based nanozymes with glutathione peroxidase like activity could effectively inhibit platelet aggregation and reduce thromboembolic risks in experimental models. Despite their potential, nanozymes face two main challenges: low catalytic efficiency due to limited active sites, and complex structures that hinder understanding of their catalytic mechanisms and rational design. Recently, single atom nanozymes (SAzymes) represent a promising advancement. With atomically dispersed metal centres, they combine the benefits of both homogeneous and heterogeneous catalysis and show high catalytic activity like natural enzymes. Iron nitrogen carbon (Fe-N-C) based SAzymes have already shown success in cancer therapy, but issues related to targeting and stability remain unresolved. To overcome these challenges, our aim is to develop a multifunctional hybrid platform integrating Fe–N–C SAzymes with mitochondria-targeting peptides (e.g., SS-31) and biocompatible polymeric carriers such as Dextran-poly(methacrylamide), guided by Prof. Mugesh’s leadership and supported by Dr. Puja’s expertise. While targeting peptides enable site-specific delivery, they are prone to degradation and instability. Incorporating polymer carriers helps protect the peptides, while also improving delivery efficiency, circulation time, and overall therapeutic performance. It is hypothesized that this all-in-one platform will outperform current technologies by effectively mitigating ROS-induced damage and thrombotic events in ischemic stroke. The principal outcome of this project is to advance this multifunctional nanozyme platform to Technology Readiness Level 4, establishing a solid foundation for preclinical validation and future translational development in the treatment of ischemic stroke.