Intermolecular Noncovalent Locks Enable Red-Shifted Emission, Modulated Reactive Oxygen Species Generation Pathway, and Shuttle-Like Nanoassembly for Phototheranostics.

Developing phototheranostic agents that combine high reactive oxygen species (ROS) generation, favorable fluorescence wavelength and intensity, and prolonged tumor retention remains a major challenge. Although molecular engineering enables precise tuning of molecular structures and properties, it often relies heavily on tedious organic synthesis. Herein, we introduce an intermolecular noncovalent locking strategy to construct systems with optimized photophysical properties for efficient phototheranostics. Aggregation-induced emission luminogens and aggregation-caused quenching luminogens are locked together to construct via multiple noncovalent interactions (e.g., C-H···N, C-H···S, S/O···N, etc.), suppressing π-π stacking and enhancing fluorescence, while intermolecular charge transfer induces a red-shifted emission and modulates ROS generation pathway. The strong intermolecular noncovalent locks also enforce tight molecular packing, leading to the formation of shuttle-like nanoassemblies rather than conventional nanospheres. Notably, this morphology enables effective tumor accumulation, prolonged retention, and highly efficient phototherapeutic outcome, achieving >90% tumor inhibition with a single injection. The proposed "intermolecular noncovalent locks" approach thus offers a paradigm for the development of advanced phototheranostic agents.