Donor/π‐Bridge Manipulation for Constructing a Stable NIR‐II Aggregation‐Induced Emission Luminogen with Balanced Phototheranostic Performance**

Abstract Owing to their versatile functionality and tunable energy dissipation, aggregation‐induced emission luminogens (AIEgens) have emerged as a potential platform for multimodal theranostics. Nevertheless, the construction of AIE‐active phototheranostic agents in the second near‐infrared window (NIR‐II, 1000–1700 nm), which allows superior resolution and minimized photodamage, is still a formidable challenge. Herein, benzo[ c ]thiophene serves as an electron‐rich and bulky donor (D)/π‐bridge, which can enlarge the conjugation length and distort the backbone of an AIEgen. By precise D/π‐bridge engineering, highly stable NIR‐II AIEgen DPBTA‐DPTQ nanoparticles are obtained with acceptable NIR‐II fluorescence quantum yield and excellent photothermal conversion efficiency. In addition, the spatial conformation of DPBTA‐DPTQ is determined for the first time by X‐ray single crystal diffraction and theoretical simulations. DPBTA‐DPTQ NPs have good biocompatibility and show efficient photothermal therapeutic effects in in vitro tests. Furthermore, DPBTA‐DPTQ NPs were used in fluorescence‐photoacoustic‐photothermal trimodal imaging‐guided photothermal eradication of tumors in HepG2 and B16‐F10 tumor‐xenografted mice.