Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma.

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2024-10-31 DOI:10.1038/s41467-024-53646-y

Hanchen Zhang, Nicolás Montesdeoca, Dongsheng Tang, Ganghao Liang, Minhui Cui, Chun Xu, Lisa-Marie Servos, Tiejun Bing, Zisis Papadopoulos, Meifang Shen, Haihua Xiao, Yingjie Yu, Johannes Karges

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引用次数: 0

Abstract

The majority of anticancer agents have a reduced or even complete loss of a therapeutic effect within hypoxic tumors. To overcome this limitation, research efforts have been devoted to the development of therapeutic agents with biological mechanisms of action that are independent of the oxygen concentration. Here we show the design, synthesis, and biological evaluation of the incorporation of a ruthenium (Ru) catalyst into polymeric nanoreactors for hypoxic anticancer therapy. The nanoreactors can catalyze the oxidation of glutathione (GSH) to glutathione disulfide (GSSG) in hypoxic cancer cells. This initiates the buildup of reactive oxygen species (ROS) and lipid peroxides, leading to the demise of cancer cells. It also stimulates the overexpression of the transient receptor potential melastatin 2 (TRPM2) ion channels, triggering macrophage activation, leading to a systemic immune response. Upon intravenous injection, the nanoreactors can systemically activate the immune system, and nearly fully eradicate an aggressive osteosarcoma tumor inside a mouse model.

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利用钌纳米反应器对缺氧性骨肉瘤进行肿瘤靶向谷胱甘肽氧化催化。

大多数抗癌药物在缺氧肿瘤中的治疗效果都会减弱，甚至完全丧失。为了克服这一限制，研究人员一直致力于开发具有独立于氧气浓度的生物作用机制的治疗药物。在这里，我们展示了将钌（Ru）催化剂加入聚合物纳米反应器用于缺氧抗癌治疗的设计、合成和生物学评估。这种纳米反应器能催化缺氧癌细胞中的谷胱甘肽（GSH）氧化为二硫化谷胱甘肽（GSSG）。这将引发活性氧（ROS）和脂质过氧化物的积累，导致癌细胞死亡。它还能刺激瞬时受体电位美拉辛 2（TRPM2）离子通道的过度表达，引发巨噬细胞活化，导致全身性免疫反应。经静脉注射后，纳米反应器可系统激活免疫系统，并几乎完全根除小鼠模型中的侵袭性骨肉瘤肿瘤。

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

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.