Research advances in metal-complex-based photosensitizers for photodynamic antimicrobial therapy

Abstract

Antimicrobial resistance has become a formidable global public health threat, with traditional antibiotic development lagging far behind the emergence of drug-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising non-antibiotic alternative due to its low resistance propensity and spatiotemporal controllability. Inspired by this, metal complex-based photosensitizers have attracted extensive research attention owing to their high chemical stability, efficient reactive oxygen species generation, and tunable photophysical properties. This review summarizes the fundamental mechanisms of metal complex-mediated aPDT, and conducts an in-depth analysis of structure-activity relationships from the perspectives of metal center selection and ligand engineering. It summarizes targeted design strategies against conventional pathogens, bacterial biofilms, intracellular bacteria, and intratumoral bacteria, with special emphasis on their applications in localized infections such as burn wounds and diabetic foot ulcers. Additionally, it outlines current key challenges including insufficient deep tissue penetration and poor hypoxic adaptability, and proposes future development directions, providing valuable references for the design and clinical translation of novel antibacterial photosensitizers. Overall, this review highlights the great potential of metal complex-based photosensitizers as next-generation antibacterial agents, and underscores that rational molecular design combined with optimized delivery systems and irradiation strategies will accelerate their clinical translation from laboratory research to clinical practice for the effective treatment of bacterial infections.