Breaking the heavy-atom paradigm: weak-donor-engineered triplet harvesting in BODIPY photosensitizers for immunogenic pyroptosis therapy
Hyeong Seok Kim, Hyeonji Rha, Mohammad Izadyar, Supphachok Chanmungkalakul, Haiqiao Huang, Yi Young Kang, Jae‐Won Ka, Yunjie Xu, Mingle Li, Xiaogang Liu, Jong Seung Kim
Abstract
-mediated spin-orbit charge-transfer intersystem crossing (SOCT-ISC). The resulting photosensitizer, Cbz-Bth-BDP, demonstrates effective reactive oxygen species generation and the photocatalytic transformation of biomolecules such as nicotinamide adenine dinucleotide (NADH) and cytochrome c (Cyt c). Notably, Cbz-Bth-BDP induces pyroptosis by activating gasdermin E (GSDME), leading to cell swelling and the release of intracellular content. In a 3D tumor spheroid model, Cbz-Bth-BDP significantly inhibits tumor growth by reducing adenosine triphosphate (ATP) levels. This study highlights the advantages of accessing higher excited triplet states and positions Cbz-Bth-BDP as a promising, heavy-atom-free photosensitizer for cancer treatment through pyroptosis activation.