Two in one: Acceptor engineering strategy to construct efficient type I aggregation induced emission photosensitizer for photodynamic antitumor and antibacterial therapy

Photodynamic therapy (PDT), operates through a distinctive reactive oxygen species (ROS)-mediated cytotoxic mechanism, offering therapeutic potential against malignant tumors and bacterial infections. The development of multifunctional photosensitizers (PSs) capable of simultaneously exhibiting potent antitumor and antibacterial activities represents a promising yet challenging frontier in PDT research. Herein, three donor-π bridge-acceptor (D-π-A) aggregation induced emission (AIE) photosensitizers TPTM , TPTP and TPTQ with type I and type II ROS production abilities were successfully constructed by acceptor engineering strategy. TPTP stands out from others by advantages of rapid cellular internalization behavior, potent ROS production capacity, dual-organelle targeting (mitochondria and endoplasmic reticulum) ability. TPTP displayed antitumor effects in 4T1 tumor-bearing nude mice, inducing ROS-mediated apoptosis and suppressing tumor growth. Simultaneously, TPTP enhanced its affinity for bacteria through its cationic part, and exhibited potent antibacterial activity against Gram-positive (G+) bacteria Staphylococcus aureus ( S. aureus ), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis ( S. epidermidis ), and Gram-negative (G−) bacteria Escherichia coli ( E. coil ) and Acinetobacter baumannii ( A. baumannii ) upon light irradiation. TPTP also performed well in promoting infected wounds healing. This work provides a versatile molecular platform for future applications in infectious diseases and oncology, with potential for further applications in combination therapies.