Research Projects

Oxidative stress is caused by increased levels of reactive oxygen species (ROS) and it plays a main role in the pathogenesis of diseases such as cancer, neurodegeneration, diabetes, and cardiovascular disorders. Although bulk antioxidant supplements provide some relief, they mostly suffer from poor specificity, saturation, and even show pro-oxidant effects, which are generally harmful. Antioxidant nanozymes, nanomaterials that mimic natural enzymes like catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) have caught significant attention as promising candidates due to their stability and catalytic antioxidant potential. Remarkably, nanozymes were very recently recognized by the prestigious World Economic Forum as one of the top 10 emerging technologies of 2025. However, most current nanozymes feature open surface, poorly-defined active sites that lack proper coordination spheres. Such features projects low substrate specificity and unintended antagonistic oxidase/peroxidase side activities, thereby raising future challenges and safety concerns for biomedical applications. To date, there are no systematic approaches reported to advance substrate selectivity or to profile side reactivity of antioxidant nanozymes. The lack of catalytic precision can lead to abnormal interactions with crucial biomolecules, interfering with key cellular processes and compromising therapeutic outcomes. This project aims to address these challenges by rational engineering nanozymes with confined, antioxidant enzyme-like active sites using metal-organic framework (MOF) cages as structural platforms. The main hypothesis is that installing well-defined catalytic centers, such as transition metal complexes and GPx mimetic organoselenium compounds, within MOF pores will facilitate selective antioxidant catalysis while minimizing side reactivities and antagonistic enzyme activities. MOFs like MOF-808, NU-1000, and ZIF-8 are chosen in this project for their tunable porosity, accessible node sites, and large internal surface area and volume, and smaller pore window, which make them ideal platforms for installing catalytically active units in a spatially confined manner. Scientific Objectives: 1. To synthesize antioxidant enzyme-like active site installed MOFs for mimicking CAT, SOD, and GPx. 2. To characterize the structure and coordination environment of active sites using sophisticated spectroscopic and microscopic tools. 3. To evaluate catalytic activity and substrate selectivity via standard ROS-scavenging assays. 4. To evaluate side reactivity (e.g., oxidase/peroxidase activity) and its consequences using in vitro and panel of cellular models. The experimental approach involves MOF functionalization with catalytically active complexes and organoselenium compounds followed by in vitro evaluation of their antioxidant enzyme-like activities. Side reactivity profiling will be performed to evaluate off-target reactions and its consequences. Cellular assays will determine cytoprotective efficacy, gene expression profiles and oxidative damage prevention. This project is expected to transform nanozymes that combine high catalytic precision with minimal off-target effects—crucial features for biological and therapeutic applications. The novelty lies in integrating organoselenium compounds and metal complexes motifs within MOF cages to facilitate substrate-selective ROS detoxification, while systematically studying their side reactivity profiles. The insights from this work will help bridge a critical gap in nanozyme design and establish valuable principles for the development of safer, next-generation antioxidant nanozymes.