Coordination-Induced Supramolecular Assembly Enhances Singlet Oxygen Generation in Pt-BODIPY Photosensitizers for Synergistic Chemo-Photodynamic Therapy

Organic dyes hold great potential as photosensitizers for tumor diagnosis and therapy. However, their practical application is hindered by two major limitations: aggregation-caused fluorescence quenching (ACQ) and inefficient reactive oxygen species (ROS) generation. To overcome these challenges, we developed a coordination-induced supramolecular assembly strategy aiming at enhancing their photophysical properties and therapeutic efficacy. Herein, two Pt(II)-BODIPY conjugates were designed by integrating platinum(II) moieties with a tailored boron-dipyrromethene derivative (py-BDP). Notably, the conjugates exhibited negligible singlet oxygen (¹O₂) production in the monomeric state, but boosted ¹O₂ generation upon aggregation. Mechanistic studies revealed that intermolecular electronic coupling during aggregation promotes efficient intersystem crossing (ISC) by narrowing the singlet-triplet energy gap (Δ<i>E</i>_ST), thereby significantly enhancing ¹O₂ generation. Moreover, the well-defined spatial structure of platinum(II) moieties effectively suppressed tightly packed intermolecular interaction between py-BDP molecules, thereby alleviating the ACQ effect and allowing for simultaneous bioimaging and therapy. In vitro biological evaluations revealed that these conjugates exhibited significant cytotoxicity against A549 cells via mitochondrion-targeted synergistic chemo-photodynamic therapy. Overall, the metalation of organic dyes offers new prospects for developing supramolecular photosensitizers with aggregation-enhanced ¹O₂ generation, providing a mechanistic perspective beyond conventional heavy-atom-effect strategies.