Kim Hyeong Seok, Rha Hyeonji, Izadyar Mohammad, Chanmungkalakul Supphachok, Huang Haiqiao, Kang Yi Young, Ka Jae-Won, Xu Yunjie, Li Mingle, Liu Xiaogang, Kim Jong Seung
Department of Chemistry, Korea University Seoul 02841 Korea
Advanced Functional Polymers Research Center, Korea Research Institute of Chemical Technology Daejeon 34114 Korea.
Chem Sci. 2025 Jul 14. doi: 10.1039/d5sc03466c.
Boron-dipyrromethene (BODIPY)-based dyes emerge as promising agents for phototherapy; however, traditional methods to enhance spin-orbit coupling (SOC) through halogenation introduce dark toxicity and limit therapeutic applications. Here, we present a thiophene-bridged BODIPY functionalized scaffold with carbazole-benzothiophene (Cbz-Bth) substituents at the 2,6-positions. This design employs a weak yet semi-rigid donor to destabilize charge-transfer (CT) states, enabling T-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.
基于硼二吡咯亚甲基(BODIPY)的染料成为光疗的有前景的试剂;然而,通过卤化增强自旋轨道耦合(SOC)的传统方法会引入暗毒性并限制治疗应用。在此,我们展示了一种噻吩桥联的BODIPY功能化支架,在2,6位带有咔唑 - 苯并噻吩(Cbz - Bth)取代基。这种设计采用了一个弱但半刚性的供体来使电荷转移(CT)态不稳定,从而实现T介导的自旋轨道电荷转移系间窜越(SOCT - ISC)。所得的光敏剂Cbz - Bth - BDP表现出有效的活性氧生成以及生物分子如烟酰胺腺嘌呤二核苷酸(NADH)和细胞色素c(Cyt c)的光催化转化。值得注意的是,Cbz - Bth - BDP通过激活gasdermin E(GSDME)诱导焦亡,导致细胞肿胀和细胞内内容物释放。在三维肿瘤球体模型中,Cbz - Bth - BDP通过降低三磷酸腺苷(ATP)水平显著抑制肿瘤生长。这项研究突出了获得更高激发三重态的优势,并将Cbz - Bth - BDP定位为一种有前景的、无重原子的光敏剂,用于通过焦亡激活进行癌症治疗。
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