Side-Chain Engineering of NIR-II-Emissive Aggregation-Induced Emission Luminogens to Boost Photodynamic and Photothermal Antimicrobial Therapy

The development of antibiotic resistance has made multidrug-resistant bacterial and fungal infections one of the most serious health problems worldwide. Photothermal therapy (PTT) and photodynamic therapy (PDT) have received increasing attention in antimicrobial fields due to their precision treatment and less susceptibility to inducing resistance. In particular, developing second near-infrared (NIR-II, 1000-1700 nm)-emissive semiconducting polymers for phototheranostics is highly desirable but remains challenging due to the lack of rational molecular design guidelines. Herein, a precise side-chain engineering strategy based on donor-acceptor (D-A)-type semiconductor polymers is developed for antimicrobial phototherapy. By subtle regulation of the side-chain flexibility, a series of NIR-II-emissive polymer aggregation-induced-emission (AIE) luminogens (AIEgens) are constructed. The optimal polymer PIDT(He)TBT bearing flexible side chains shows optimal physicochemical properties, including the highest mass extinction coefficient, the best AIE property, red-shifted absorption/emission spectra, and desirable photodynamic and photothermal effects. PIDT(He)TBT is then encapsulated into nanoparticles to endow them with water solubility, excellent photostability, and enhanced type-I photodynamic and photothermal effects. The excellent performance of PIDT(He)TBT nanoparticles in terms of fluorescence-guided type-I PDT and PTT of bacterial and fungal infections has been demonstrated both in vitro and in vivo. This work brings useful insights into designing NIR-II-emissive semiconducting polymer AIEgens for highly efficient phototheranostics.