Multimodal antibacterial agents based on photodynamic therapy and photothermal therapy: principles, design strategies and applications.

Abstract

Antimicrobial resistance (AMR) and bacterial biofilms pose a dire global health threat. To combat localized infections (e.g., chronic wounds, implant-associated infections), multimodal strategies combining photodynamic therapy (PDT) and photothermal therapy (PTT)-collectively referred to as photoactivated therapies (PT)-have emerged as promising antibiotic-sparing photoactivated approaches. This review systematically surveys multimodal platforms that integrate PDT/PTT with chemodynamic therapy (CDT), sonodynamic therapy (SDT), gas therapy, antibiotics, and immunotherapy. We highlight the rational design of nanomaterials that enable both reactive oxygen species (ROS) generation and photothermal conversion, thereby overcoming monotherapy limitations such as poor tissue penetration, hypoxia, and low efficiency. The applications of these systems in treating chronic wounds, implant infections, and deep-seated infections are discussed, with emphasis on material innovations including aggregation-induced emission (AIE) agents, metal-organic frameworks (MOFs), and biomimetic platforms. Finally, we critically evaluate challenges in targeting precision, long-term biosafety, and clinical translation, while outlining future directions toward smart responsive systems and AI-assisted design.