Modulation of Donor and Acceptor to Construct Near-Infrared Conjugated Polymers with Type I PDT for Efficient Antibacterial Therapy.

The development of novel antibacterial strategies for the treatment of pathogenic bacterial infections is urgent. Photodynamic therapy (PDT) is considered a promising solution. However, near-infrared (NIR) type I photosensitizers are still lacking for deep-tissue infection treatment. Herein, we construct a series of donor-acceptor (D-A) NIR-conjugated polymers with type I PDT through precise molecular engineering and systematically elucidate the structure-activity relationship between D-A architecture and type I reactive oxygen species (ROS) generation capacity. First, three D-A polymers are synthesized by pairing fluorene with different acceptors, among which TQT (6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline)-based conjugated polymer (VCP3) exhibits the highest ROS generation. Subsequent donor engineering with TQT as an acceptor affords NIR-absorbing polymers. In particular, NIR-conjugated polymer NCP3, bearing 2,7-di(thiophen-2-yl)fluorene as a donor, demonstrates outstanding type I ROS generation ability. The resulting cationic NCP3 NPs achieve efficient photodynamic antibacterial performance for treating bacterial abscesses in vivo with favorable biosafety. This work provides robust molecular engineering guidelines for designing NIR type I photosensitizers toward deep-tissue antibacterial therapy.