Tuning Photophysical Conflict Into Synergy: Stereoelectronic Planarity Disruption Unlocks Concurrent Aggregation‐Enhanced ROS and NIR‐II Fluorescence

ABSTRACT The development of near‐infrared‐II (NIR‐II) fluorescent photosensitizers is fundamentally limited by a photophysical trade‐off: aggregation‐caused quenching that typically suppresses both reactive oxygen species (ROS) and fluorescence. Herein, we introduce a paradigm‐shifting strategy—stereoelectronic planarity disruption of molecular planarity—to transform this detrimental trade‐off into a synergistic, aggregation‐enhanced process. By integrating sterically demanding and electronically communicative peripheries into an acceptor–donor–acceptor–donor–acceptor (A–DA'D–A) scaffold, we designed small molecules (AS4T and AS4Se) that exhibit concurrent aggregation‐enhanced ROS and fluorescence efficiencies. This unique design, verified by theoretical and structural analyses, alleviates detrimental π–π interactions to simultaneously promote intersystem crossing and radiative decay in the aggregate state. The derived nanoparticles (NPs), particularly AS4T NPs, achieve a record‐high 1 O 2 quantum yield (24.7%), robust O 2 •− production, and 6.3‐fold higher NIR‐II brightness than ICG/FBS. Under low‐power 808 nm laser irradiation, AS4T NPs enable high‐contrast tumor imaging and complete tumor elimination through photodynamic therapy alone, even for deep‐seated tumors. This work establishes a new design paradigm that unifies aggregation‐enhanced ROS and fluorescence efficiency in NIR‐II fluorescent photosensitizers, offering a transformative approach to highly efficient tumor phototheranostics.