Near‐Infrared II AIE Luminogens with Mitochondria‐Targeting Characteristics for Combinational Phototherapies of Breast Tumors Through Synergistic Cell Apoptosis and Pyroptosis

Abstract Conventional photosensitizers for tumor phototherapy are greatly limited by their reliance on a single‐cell death process, leading to insufficient therapeutic effects and restricted biomedical applications. To address these limitations, multifunctional fluorophores, BTA and BTB, are designed based on an electron donor‐π‐acceptor system. By adjusting the strength of the intramolecular charge transfer through varying electron‐donating moieties, their optical properties are tailored. BTA emits bright near‐infrared II (NIR‐II) fluorescence and exhibits typical aggregation‐induced emission (AIE) characteristics, a large Stokes shift (>250 nm), good photostability, satisfactory biocompatibility, and remarkable mitochondria‐targeting capabilities. Notably, it demonstrates potent photodynamic and photothermal properties. BTA as an effective photosensitizer and a photothermal agent, generates various cytotoxic Type I and II reactive oxygen species and photothermal energy to effectively destroy tumor cell mitochondria and suppress tumor growth. Importantly, the molecular mechanisms underlying combination phototherapy are elucidated, revealing that it induces synergistic cell apoptosis and pyroptosis. These results highlight the potential of multifunctional AIE materials with bright NIR‐II fluorescence and mitochondria‐targeting characteristics for the synergistic phototherapy of breast tumors, offering new insights for future therapeutic developments.