Bright “D–A–D” semiconducting small molecule aggregates for NIR-II fluorescence bioimaging guiding photothermal therapy

Donor-acceptor-donor (D-A-D) semiconducting small molecule nanoparticles have emerged as high-performance NIR-II fluorophores for real-time bioimaging. However, due to their intrinsic defects in aggregation-caused quenching (ACQ) and "energy gap law", D-A-D semiconducting small molecule nanoparticles typically exhibit low NIR-II fluorescence quantum yields (QYs). Herein, both the strategies of aggregation induced emission (AIE) and intermolecular charge transfer (CT) have been incorporated into the design of new D-A-D semiconducting small molecules. AIE enhances the NIR-II fluorescence intensity of NIR-II fluorophore aggregates in nanoparticles, while intermolecular CT increases both NIR absorption and NIR-II emission, thereby further improving their NIR-II fluorescence QYs. Four D-A-D semiconducting small molecules (TD, TT, TC, and TCD) were designed. Due to the combination of intermolecular CT and AIE of TCD aggregates, the NIR absorption and NIR-II fluorescence signals of TCD NPs were stronger than those of TD NPs and TT NPs with a single AIE property or TC NPs with strong intermolecular CT. Furthermore, TCD NPs demonstrated excellent performance in <i>in vivo</i> NIR-II fluorescence bioimaging guiding photothermal therapy.