A Dual‐Acceptor Engineered Second Near‐Infrared Ionic Aggregation‐Induced Emission Luminogen for Mitochondria‐Disrupted Cancer Phototheranostics

ABSTRACT Ionic phototheranostic agents have found extensive application in preclinical and clinical practice owing to their excellent biocompatibility and synergistic diagnostic–therapeutic integration. However, they still suffer from certain limitations, such as short absorption/emission wavelengths, poor photostability, aggregation‐caused fluorescence self‐quenching, and diminished phototherapeutic efficacy upon aggregation, which collectively hinder their efficacy in complex clinical scenarios. To address these challenges, a second near‐infrared (NIR‐II) ionic phototheranostic agent, namely DT‐BT‐BIn, is rationally designed and synthesized via an innovative dual‐acceptor engineering strategy. DT‐BT‐BIn ingeniously integrates benzothiadiazole and benzo[ c,d ]indolium as dual‐acceptor units, which successfully achieves superior aggregation‐induced NIR‐II emission characteristics, highly efficient Type I/II photodynamic activity coupled with photothermal effect, and excellent photostability. Moreover, the self‐assembled DT‐BT‐BIn nanoprobes (NPs) can be effectively internalized by cancer cells in vitro. Under irradiation, DT‐BT‐BIn NPs are capable of disrupting mitochondrial membrane potential, thereby inducing apoptotic cell death. Furthermore, in vivo investigations demonstrate DT‐BT‐BIn NPs can effectively accumulate at tumor location, enabling NIR‐II fluorescence/photothermal imaging‐guided precise tumor ablation, while simultaneously maintaining favorable biosafety toward normal tissues. Collectively, this study underscores the considerable promise of the dual‐acceptor strategy in constructing high‐performance NIR‐II ionic phototheranostic agents and provides a new avenue for clinical precision cancer phototherapy.