Research Projects

The alarming rise of antimicrobial resistance (AMR) poses a critical challenge in the post-antibiotic era. Microbes have developed sophisticated defense mechanisms, including the formation of biofilm matrices that resist conventional antibiotics. This highlights a significant knowledge gap in combating AMR, necessitating innovative, cross-disciplinary therapeutic strategies. Antimicrobial nanosystems have recently gained attention for their potential to overcome resistance through tunable physicochemical properties and polyvalent interactions. Photocatalytic inactivation of drug-resistant microbes using inorganic semiconductors has also shown promise, yet it primarily targets planktonic bacteria and fails to address virulent biofilm eradication effectively. This underscores the need for nanosystems tailored to the complex redox microenvironment of bacterial biofilms, paving the way for transformative AMR research. The proposed project, PeV_BioCat, aims to develop an NIR-light-active heterojunction nanosystem based on lanthanide ion-doped perovskite nanoclusters coupled with graphitic carbon nitride (LnPeV/g-CN). This ternary nanosystem will incorporate single-atom/cluster catalytic sites (Fe, Co) on the g-CN shell to achieve efficient multimodal therapy, including chemodynamic therapy (CDT), photocatalytic therapy (PCT) and Immunotherapy (IMT). By leveraging a novel mechanistic pathway inspired by biocatalytic reactions and metalloenzyme’s functions, the system will selectively target and disrupt biofilm matrices in lung infections associated with chronic pulmonary diseases and tuberculosis. The nanosystem design features: 1. Bioorthogonal Catalytic Activation: Selective photocatalytic activation of biofilm-forming biomolecules within lung infections. 2. Targeted Delivery: Specific ligands (e.g., mannose/amphipathic molecules) ensure active targeting of bacterial biofilms in lung fibroblasts. 3. Operando Spectroscopic Insights: Advanced spectroscopy, microscopy, and molecular microbiology tools to elucidate structure-activity relationships and maximize catalytic efficiency. 4. End Usage: Development of inhaling spray aerosol of perovskite heterojunctions to be targeted into mice lungs and NIR activation (biological window light) of materials by non-invasive means. This innovative approach addresses critical knowledge gaps in biofilm-targeted antibacterial therapy, offering a versatile solution applicable to AMR-related lung infections, including Mycobacterium tuberculosis, Klebsiella pneumoniae, and chronic obstructive pulmonary disease (COPD). Additionally, the system’s relevance to lung infections arising from air pollution emphasizes its broader impact, particularly in India’s context. The project seeks to redefine AMR treatment through a sophisticated, multidisciplinary framework, advancing both scientific understanding and clinical solutions.