A synergistic platform integrating iodinated BODIPY photosensitizers and microglial cells for superior photodynamic antibacterial efficacy.

Alzheimer's disease (AD) is closely linked to gut dysbiosis and microbial translocation, highlighting an urgent need for antimicrobial strategies that combine high efficiency with host immune compatibility. Photodynamic therapy using photosensitizers offers a promising approach, yet conventional agents often lack the ability to engage host defense mechanisms for sustained bacterial clearance. Here, we report a synergistic platform that integrates iodinated BODIPY-based photosensitizers with BV-2 microglial cells to achieve enhanced antibacterial efficacy through the cooperative action of photodynamic killing and microglial phagocytosis. A series of BODIPY derivatives bearing iodine atoms at the 2,6-positions and functionalized with isocyano or aldehyde groups at the meso-position were synthesized. Among them, NC-PhBDP-I exhibits both stable and rapid reactive oxygen species (ROS) generation capacity and negligible cytotoxicity, positioning it as an ideal candidate for synergistic application. Mechanistically, photodynamic treatment with NC-PhBDP-I not only induces rapid bacterial membrane disruption but also potently activates BV-2 microglial phagocytic activity, leading to accelerated clearance of residual bacteria that survive the initial photodynamic insult. This dual-modal action results in a pronounced synergistic effect, with the combination markedly surpassing the sum of individual effects from photodynamic treatment or microglial engagement alone. Our findings establish an integrated chemical-biological platform that leverages both photodynamic and innate immune functions, offering a promising strategy for combating bacterial infections in the context of AD and beyond.