An Activable Photosensitizer for Sunshine‐Driven Photodynamic Therapy Against Multiple‐Antibiotic‐Resistant Bacteria by Exploiting Macrophage Chemotaxis

Aiming to improve photodynamic therapy (PDT) safety and specificity at the in vivo level, a new concept is proposed by combining the chemotaxis and circulating ability of macrophages with the controllable therapeutic efficiency of PDT. Moreover, an irradiation strategy is utilized of sunbathing to conduct PDT. Specifically, an inflammation-activable photosensitizer (Lyso710A) based on NIR BODIPY is designed and loaded it into macrophages. These "armed" macrophages are then transferred into the infected host to capture bacteria and transport them to the surface of the skin through blood circulation, where sunlight can penetrate. Upon capturing bacteria, the photodynamic effect of Lyso710A is turned on by the macrophage's endogenous hypochlorous acid (HClO). When these macrophages reach the epidermis, the bacteria are eradicated by the photodynamic effect of the activated photosensitizer during exposure to sunlight. Furthermore, this strategy demonstrates promising therapeutic efficacy in two animal models (mouse and rabbit) with systemic bacterial infection, using a low photosensitizer dose of 0.14 mg Kg^-1 in animals. This work demonstrates an intelligent and promising approach to breaking the routine of PDT and, for the first time, executing PDT for deep-tissue bacterial infection simply by bathing in the sunshine.