Nanoenzyme-Enhanced Catalytic Photodynamic Therapy for Cancer

Catalytic photodynamic therapy is an emerging strategy that integrates enzyme-mimetic nanomaterials with photosensitisers to overcome the intrinsic limitations of conventional photodynamic therapy in solid tumours. Conventional photodynamic therapy relies on the oxygen-dependent generation of cytotoxic reactive oxygen species, which is severely compromised by tumour hypoxia, elevated antioxidant defences, heterogenous photosensitiser accumulation, and limited light penetration. Nanoenzyme-mediated catalytic photodynamic therapy addresses these barriers through two mechanistically distinct catalytic modes: oxygen-generating catalytic photodynamic therapy, in which catalase-like nanoenzymes disproportionate endogenous hydrogen peroxide into molecular oxygen to sustain Type II photochemistry, and oxygen-independent catalytic photodynamic therapy, in which peroxidase/Fenton-like nanoenzymes convert hydrogen peroxide into hydroxyl radicals without requiring oxygen or light activation. Multi-enzyme cascade systems integrate both modes, enabling synergistic reactive oxygen species generation across heterogenous tumour regions. This review discusses the catalytic mechanisms, nanoenzyme classes, including carbon-based materials, metal–organic frameworks, plasmonic nanostructures, and biomimetic systems, and therapeutic applications of catalytic photodynamic therapy. We critically evaluate the evidence linking catalytic activity to improved photodynamic outcomes, highlight methodological limitations in reactive oxygen species assessment, and examine translational challenges including substrate heterogeneity, colloidal scalability, uncontrolled reactive oxygen species generation, and regulatory hurdles. Emerging research directions, including artificial intelligence-mediated nanomaterial design, quantum-guided catalytic optimisation, and immunoengineering, are considered as strategies to accelerate clinical translation.