Synthesis and Application of a Novel Multifunctional Nanoprodrug for Synergistic Chemotherapy and Phototherapy with Hydrogen Sulfide Gas

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-01-09 DOI:10.1021/acs.jmedchem.4c02426

Silan Yang, Yijun Liu, Tianyu Wu, Xuan Zhang, Shan Xu, Qingshan Pan, Lianghui Zhu, Pengwu Zheng, Dan Qiao, Wufu Zhu

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引用次数: 0

Abstract

With the dilemma of limited efficacy of individual therapies, it is crucial to develop innovative combination therapy systems to target the complex pathogenesis of cancer. In this study, we designed a nanoprodrug ISL@MIL-101-ADT to facilitate synergistic delivery of hydrogen sulfide (H₂S) and prodrug ISL for specific eradication of tumor cells with minimal toxicity and maximal efficacy. The nanoprodrug passively targeted tumors through enhanced permeation and retention effects, followed by disintegration and release of IR780, lonidamine (LND), and H₂S. IR780 localizes LND to mitochondria to enhance therapeutic effects and turn on the phototherapy and chemotherapy when exposed to a laser; H₂S inhibits procancer signaling pathways and mitochondrial function. In vivo experiments have demonstrated that ISL@MIL-101-ADT exhibits excellent pharmacokinetic properties and significant tumor inhibitory effects. Additionally, this nanoprodrug possesses outstanding photothermal and fluorescence imaging capabilities. Therefore, we strongly believe that the nanoprodrug present herein holds great potential for application in cancer therapy.

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硫化氢气体协同化疗光疗的新型多功能纳米前体药物的合成与应用

面对单方治疗疗效有限的困境，针对复杂的癌症发病机制，开发创新的联合治疗系统至关重要。在这项研究中，我们设计了一种纳米前药ISL@MIL-101-ADT，以促进硫化氢（H2S）和前药ISL的协同递送，以最小的毒性和最大的功效特异性根除肿瘤细胞。纳米前药通过增强渗透和滞留效应被动靶向肿瘤，随后分解和释放IR780、lonidamine （LND）和H2S。IR780将LND定位于线粒体以增强治疗效果，并在暴露于激光时开启光疗和化疗；H2S抑制procancer信号通路和线粒体功能。体内实验表明ISL@MIL-101-ADT具有良好的药代动力学特性和显著的肿瘤抑制作用。此外，该纳米前药具有出色的光热和荧光成像能力。因此，我们坚信纳米前药在癌症治疗中具有巨大的应用潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.