Space-Arranged Intramolecular Modular Assembled Dyad as Superior-Performance “Superoxide Anion Engine” for Boosting Photodynamic Therapy

Tumor photodynamic therapy (PDT) has lauded the photosensitizers (PSs), yet their performance in most hypoxic tumors is still far from being satisfactory. In this effort, inspired by the unprecedented efficiency of natural photosynthesis, we propose an intramolecular modular assembled (iMMA) strategy to improve photosensitization based on off-the-shelf chromophores. Specifically, we built a π-stacking dyad PS-An from PS chromophore with intrinsically wide absorption and triplet property aligned with An chromophore. PS-An showed an impressive extension in excited state lifetime from 20.6 μs (PS) to 0.79 ms and a full charge separation, which not only increased the sensibility to O2 but also boosted the dominant superoxide anion (O2•–) production in the Type I process. Moreover, it proved its success in boosting Type I PDT efficiency of cancer cell under hypoxic conditions and solid tumors in mice. This is the first example that π-stacking iMMA strategy is used to regulate the PSs to boost the Type I photosensitization.