Lee Jung Hoon, Kozoriz Kostiantyn, Hong Kyung Tae, Murale Dhiraj P, An Seo Jeong, Choi Sang-Hyun, Lee Jun-Seok
Department of Pharmacology, Korea University College of Medicine, Korea University, Seoul 02841, South Korea.
Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, South Korea.
J Med Chem. 2025 May 22;68(10):9947-9957. doi: 10.1021/acs.jmedchem.4c02633. Epub 2025 Jan 31.
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.
光动力疗法（PDT）提供了微创且可重复的癌症治疗选择。尽管在光敏剂（PS）设计方面取得了进展，但PS激活的光学控制仍未得到探索。在此，我们展示了首个基于BOAHY-硼二吡咯二元体系的光开关PS。受硼二吡咯多聚体结构和BOAHY光异构化特性的启发，我们设计了单（4系列）和双BOAHY-硼二吡咯（5系列）共轭物。这些二元体在白光下主要通过I型过程产生活性氧物种。值得注意的是，4系列化合物在体外表现出有效的光细胞毒性和光开关特性。在此基础上，我们对单共轭物进行碘化以开发高效的光开关PS 6b，由于单线态-三线态能隙减小，其表现出增强的系间窜越和II型活性氧物种生成。作为光开关PDT剂的首次展示，该策略引入了一种具有选择性癌症治疗和临床应用巨大潜力的新方法。
