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打破重原子范式:用于免疫原性细胞焦亡治疗的BODIPY光敏剂中弱供体工程化三线态捕获

Breaking the heavy-atom paradigm: weak-donor-engineered triplet harvesting in BODIPY photosensitizers for immunogenic pyroptosis therapy.

作者信息

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

机构信息

Department of Chemistry, Korea University Seoul 02841 Korea

Advanced Functional Polymers Research Center, Korea Research Institute of Chemical Technology Daejeon 34114 Korea.

出版信息

Chem Sci. 2025 Jul 14. doi: 10.1039/d5sc03466c.


DOI:10.1039/d5sc03466c
PMID:40687695
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12273498/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/e235650fa10d/d5sc03466c-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/eb9f8d34e560/d5sc03466c-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/cd718534d71d/d5sc03466c-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/9ae156d2837a/d5sc03466c-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/dc140f45f9a3/d5sc03466c-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/740404686da0/d5sc03466c-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/43a7aceb7ac0/d5sc03466c-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/e235650fa10d/d5sc03466c-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/eb9f8d34e560/d5sc03466c-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/cd718534d71d/d5sc03466c-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/9ae156d2837a/d5sc03466c-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/dc140f45f9a3/d5sc03466c-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/740404686da0/d5sc03466c-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/43a7aceb7ac0/d5sc03466c-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58d/12376829/e235650fa10d/d5sc03466c-f6.jpg

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[1]
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[9]
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本文引用的文献

[1]
Aggregate Science: from Molecules, beyond Molecules.

Adv Mater. 2025-1

[2]
The Photodynamic Agent Designed by Involvement of Hydrogen Atom Transfer for Enhancing Photodynamic Therapy.

Angew Chem Int Ed Engl. 2025-1-2

[3]
Devising Biocompatible, NIR-Activated Helical Pyroptosis Agents via 𝛑-Twisting Strategy for Promoting Antitumor Immunity.

Small. 2024-12

[4]
Heavy-atom-free triplet benzothiophene-fused BODIPY derivatives for lipid droplet-specific biomaging and photodynamic therapy.

Chem Commun (Camb). 2024-9-5

[5]
Controlling cellular packing and hypoxia in 3D tumor spheroids DNA interactions.

Biomater Sci. 2024-9-10

[6]
Bioinspired AIE Nanomedicine: A Burgeoning Technology for Fluorescence Bioimaging and Phototheranostics.

Adv Mater. 2024-8

[7]
Oxidative photocatalysis on membranes triggers non-canonical pyroptosis.

Nat Commun. 2024-5-13

[8]
Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Adv Mater. 2024-7

[9]
Unsymmetrical Benzothieno-Fused BODIPYs as Efficient NIR Heavy-Atom-Free Photosensitizers.

J Org Chem. 2024-4-5

[10]
Lutetium texaphyrin: A photocatalyst that triggers pyroptosis via biomolecular photoredox catalysis.

Proc Natl Acad Sci U S A. 2024-2-27

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