Abstract
ABSTRACT
Type‐I photosensitization addresses the dilemma of intracellular bacterial hypoxia‐induced photodynamic therapeutic (PDT) inefficacy, yet precise targeting and eradicating sequestered pathogens remains a formidable challenge. Herein, we engineer an albumin‐based photodynamic conversion nanoparticles integrating target‐specific recognition with controlled antibacterial functions to precisely eliminate intracellular pathogens and restore infected cell activity. Mechanistic studies reveal a vertically‐crossed conformation that promotes intramolecular electron transfer and charge separation, redirecting photosensitizer (PS) reactivity toward type‐I reactive oxygen species (ROS) generation. Electron‐rich albumin further enhances cationic PS
+•
recycling, photostability, and O
2
−•
production, while its selective cytoplasmic delivery via receptor/charge interactions enables preferential accumulation in intracellular bacteria, with reduced off‐target organelle engagement. We demonstrate application in
S. aureus
‐infected sepsis showing high type‐I ROS levels for antibacterial function from the nanoparticles to restore redox and immune homeostasis without noticeable toxicity. This work pioneers a conformationally‐gated ROS conversion approach for eliminating intracellular bacterial infections, merging mechanistic precision with therapeutic potential for clinical sepsis management.