Dyad System of BOAHY-BODIPY Conjugates as Novel Photoswitchable Photosensitizers for Photodynamic Therapy

Photodynamic therapy (PDT) offers minimally invasive and repeatable cancer treatment options. Despite advancements in photosensitizer (PS) design, the optical control of PS activation remains unexplored. Here, we present the first photoswitchable PS based on a BOAHY-BODIPY dyad system. Inspired by BODIPY multimer structures and BOAHY's photoisomerization properties, we designed mono-(4 series) and bis-BOAHY-BODIPY (5 series) conjugates. These dyads primarily generate reactive oxygen species via a type-I process under white light. Notably, the 4 series compounds demonstrated effective photocytotoxicity and photoswitching properties in vitro. Building on these, we iodinated the monoconjugates to develop the highly efficient photoswitching PS, 6b, which exhibited enhanced intersystem crossing and type-II reactive oxygen species generation due to a reduced singlet-triplet energy gap. As the first demonstration of photoswitchable PDT agents, this strategy introduces a new approach with significant potential for selective cancer treatment and clinical applications.