Synergistic Photodynamic and Chemodynamic Therapy for Tumor Treatment Using a Glutathione-Activated Photosensitizer with Near-Infrared (NIR) Imaging

IF 11.3 1区化学 Q1 CHEMISTRY, PHYSICAL ACS Catalysis Pub Date : 2024-09-10 DOI:10.1021/acsmaterialslett.4c0140010.1021/acsmaterialslett.4c01400

Fan Zheng, Duoyang Fan, Heying Yao, Jipeng Ding, Shuai Huang, Yanpeng Fang, Jie Dong, Fei Chen and Wenbin Zeng*,

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Abstract

Photodynamic therapy (PDT) utilizes photosensitizers (PSs) to generate cytotoxic reactive oxygen species (ROS) upon irradiation, leading to cell death. However, conventional PSs can cause unwanted side effects. Activatable photosensitizers (aPSs) offer a solution by remaining inactive until triggered within tumor microenvironment. Here, we present HFP-SS-Fc, a novel glutathione (GSH) aPS that leverages the high GSH concentration in tumors. HFP-SS-Fc exhibits potent near-infrared (NIR) fluorescence and a robust photodynamic effect upon exposure to tumor-specific GSH levels. A disulfide bond links ferrocene to HFP-SS-Fc, quenching NIR emission and hindering ROS generation. This ferrocene moiety also facilitates •OH production and O₂ release through a Fenton-like reaction, maintaining efficacy in hypoxic tumors. Inspired by its theranostic potential in vitro, HFP-SS-Fc successfully achieves real-time tumor imaging and significant tumor growth inhibition in vivo. This study has presented HFP-SS-Fc as a promising tool for synergistic PDT and CDT with minimized side effects, guided by NIR fluorescence.

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利用谷胱甘肽激活的光敏剂和近红外成像技术协同光动力疗法和化学动力疗法治疗肿瘤

光动力疗法（PDT）利用光敏剂（PSs）在照射时产生细胞毒性活性氧（ROS），导致细胞死亡。然而，传统的光敏剂会产生不必要的副作用。可活化光敏剂（aPSs）提供了一种解决方案，它在肿瘤微环境中被触发前保持非活性。在这里，我们介绍一种新型谷胱甘肽（GSH）aPS--HFP-SS-Fc，它利用了肿瘤中较高的GSH浓度。HFP-SS-Fc 具有强效的近红外（NIR）荧光，暴露于肿瘤特异性的 GSH 水平时可产生强大的光动力效应。二硫键将二茂铁与 HFP-SS-Fc 连接起来，淬灭了近红外发射，阻碍了 ROS 的生成。这种二茂铁分子还能通过类似芬顿的反应促进-OH的产生和O2的释放，从而保持对缺氧肿瘤的疗效。受其体外治疗潜力的启发，HFP-SS-Fc 成功实现了实时肿瘤成像和显著的体内肿瘤生长抑制。这项研究表明，在近红外荧光的引导下，HFP-SS-Fc 是一种副作用最小的协同光动力疗法（PDT）和光动力疗法（CDT）的理想工具。

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来源期刊

ACS Catalysis CHEMISTRY, PHYSICAL-

CiteScore

20.80

自引率

6.20%

发文量

1253

审稿时长

1.5 months

期刊介绍： ACS Catalysis is an esteemed journal that publishes original research in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. It offers broad coverage across diverse areas such as life sciences, organometallics and synthesis, photochemistry and electrochemistry, drug discovery and synthesis, materials science, environmental protection, polymer discovery and synthesis, and energy and fuels. The scope of the journal is to showcase innovative work in various aspects of catalysis. This includes new reactions and novel synthetic approaches utilizing known catalysts, the discovery or modification of new catalysts, elucidation of catalytic mechanisms through cutting-edge investigations, practical enhancements of existing processes, as well as conceptual advances in the field. Contributions to ACS Catalysis can encompass both experimental and theoretical research focused on catalytic molecules, macromolecules, and materials that exhibit catalytic turnover.