Aggregation turns BODIPY fluorophores into photosensitizers: reversibly switching intersystem crossing on-and-off for smart photodynamic therapy

We report for the first time a practical and simple supramolecular approach to turn fluorophores into photosensitizers (PSs). Using boron dipyrromethene (BODIPY) as a proof-of-concept, eight BODIPY derivatives manifest bright fluorescence and generate negligible singlet oxygen in solution. In contrast, aggregation fails to emit fluorescence and enhances singlet oxygen generation. Experimentally, these aggregates have excellent photodynamic therapy (PDT) performance, and one even exhibits much stronger photocytotoxicity than the commercialized PS Ce6 under identical conditions. Theoretical studies show that this property originated from significantly reduced energy gaps between relevant excited singlet and triplet states, leading to considerably improved intersystem-crossing efficiency. Importantly, a simple disaggregation recovers the original properties of the fluorophores. This reversible switching property between fluorophores and PSs assists the development of smart PDT systems, in which singlet oxygen generation in tumors can be controlled in an intelligent manner after PDT treatment. The present work provides a novel strategy to design heavy-atom-free PSs and may pave the way to the development of smart PDT systems.