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.