Bioinspired targeting strategies for antimicrobial photodynamic therapy.

Abstract

Bacterial infections and the escalating antimicrobial resistance crisis pose a major global health threat, positioning antimicrobial photodynamic therapy (aPDT) as a promising antibiotic-free alternative. However, the limited targeting capability of photosensitizers leads to inadequate accumulation at infection sites, suboptimal bactericidal efficacy, and off-target toxicity, which hinders their clinical translation. Bioinspired targeting strategies that emulate the intrinsic mechanisms of natural biological systems, including electrostatic adhesion, molecular recognition, metabolic exploitation, and microenvironment sensing, have emerged as effective approaches to address these challenges. Despite rapid advances, systematic reviews that classify aPDT targeting strategies from a bioinspired mechanistic perspective remain lacking. Here, we comprehensively summarize the natural prototypes, design principles, and recent material advances in bioinspired targeting for aPDT. We further conduct a comparative analysis of these strategies in terms of mechanisms, advantages, limitations, biosafety, and optimization pathways. Finally, we discuss the key obstacles to clinical translation and possible solutions, providing valuable insights for the development of innovative strategies.