Flexible Regulation of Optical Properties Based on Structure Size‐Driven Intermolecular Interactions for Phototherapy

Abstract The precise control of optical properties in molecular systems remains a challenge for phototherapy. Herein, the strategic combination of aggregation‐caused quenching (ACQ) and aggregation‐induced emission (AIE) molecule creates ACQ@AIE bimolecular systems with tunable optical properties, which are almost unattainable by single‐component materials. Through systematic investigation of three ACQ@AIE bimolecular systems, it is established that molecule structure size differentials dictate their intermolecular interactions and consequent optical behaviors. Crucially, AIE molecule with a smaller structure size promotes ACQ molecule clustering to enhance the photothermal effect, while when the size becomes larger, particularly approaching that of ACQ molecule, facilitating π–π stacking and boosting the photodynamic effect. These distinct assembly modes revealed through combined experimental and theoretical analyses, enable precise regulation of photothermal versus photodynamic effects by simply regulating the structure size and ratio of ACQ and AIE molecules. Building on these mechanistic insights, the optimal molecule combination of ACQ@AIE bimolecular system is engineered into nanoparticles that exhibit mild photothermal effect, strong photodynamic effect, and excellent tumor accumulation and retention, achieving near‐complete tumor eradication with minimal treatment cycles while maintaining good biosafety. This work not only elucidates the fundamental structure size‐interaction‐property relationships in ACQ@AIE bimolecular systems but also provides generalizable strategies for developing intelligent photo theranostic materials through controlled intermolecular interaction.