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

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 ¹O₂ quantum yield (24.7%), robust O₂ ^•- 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.