A [1,2,5]Thiadiazolo[3,4-g]quinoxaline-Based Alternating Conjugated Polymer Enables Highly Efficient Near-Infrared-II Photothermal Antibacterial Therapy

Photothermal antimicrobial therapy within the second near-infrared biological window (NIR-II, 1000–1350 nm) enables improved laser penetration depth and higher maximum permissible exposure (MPE); however, NIR-II photothermal agents (PTAs) with a high photothermal conversion efficiency (PTCE) and superior safety for this purpose remain scarce. Given the inherent merits of conjugated polymers such as excellent biocompatibility, strong light-harvesting ability, and easily tunable spectral properties, a NIR-II PTA based on a donor (D)–acceptor (A) alternating conjugated polymer, namely, poly[4,9-(6,7-bis(4-((2-octyldodecyl)oxy)phenyl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline)-alt-2,5-(thiophene)] (PTTQ), has been developed for efficient photothermal antimicrobial therapy in vitro and in vivo. PTTQ/amphiphilic polymer (DSPE-MPEG2000) composite nanoparticles (PTTQNPs) exhibit robust absorption in the NIR-II region and an outstanding PTCE of 51.7% upon irradiation with a 1064 nm laser (1 W cm–2). With excellent biocompatibility and remarkable photothermal/photo stability, PTTQNPs demonstrated an antibacterial rate of approximately 100% against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro and enabled the wounds induced by S. aureus in mice to heal almost completely. This study underscores the potential of D–A alternating conjugated polymers as NIR-II PTAs in the fight against bacterial infections while also providing valuable insights into the structural design of highly efficient NIR-II PTAs based on conjugated polymers.