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.