From plasma membrane to mitochondria: Time-dependent photodynamic antibacterial and anticancer therapy with a near-infrared AIE-active photosensitizer

• A multi-functional AIE-active photosensitizer with broad absorption and outstanding ROS sensitizing efficiency was developed. • It can be used for time- and location-dependent sequential killing of bacteria and cancer cells. • Through controlling the incubation time, it can selectively bind to the membrane of bacteria and mitochondria of cancer cells. • It exhibited potent photodynamic antibacterial performance against methicillin-resistant Staphylococcus aureus and growth retardation of solid tumors in vivo . Multi-functional photosensitizers (PSs) with time-dependent subcellular localizations for defined and multiple targets are highly desirable for smart therapy but rarely reported. Herein, a near-infrared (NIR) aggregation-induced emission (AIE)-active PS, named TBTCP , with a broad absorption band covering the whole visible spectrum and excellent reactive oxygen species (ROS) generation efficiency was designed and synthesized. Upon short time incubation, TBTCP could insert into the bacterial membrane and showed good photodynamic antibacterial performance towards both Gram-positive and Gram-negative bacteria under light irradiation. TBTCP also exhibited cancer cell selectivity in photodynamic therapy under controlled condition through TBTCP -based light-induced mitochondrial damage that activated apoptotic signaling pathways. In vivo experiments confirmed that TBTCP exhibited potent photodynamic antibacterial performance against methicillin-resistant Staphylococcus aureus (MRSA) . In cancer mice model, TBTCP -based photodynamic therapy was also effective and was superior to the widely used PS, Chlorin e6 (Ce6). This study introduced an effective and versatile PS which not only advances the clinical application of photodynamic therapy but also provides a building block for next-generation PSs.