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 (ΔEST), 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.