Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours

IF 26.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering Pub Date : 2024-07-18 DOI:10.1038/s41551-024-01239-x

Qunfeng Fu, Shuren Zhang, Siyong Shen, Zhi Gu, Junyi Chen, Dongfan Song, Pengwei Sun, Chunhong Wang, Zhibin Guo, Yunlong Xiao, Yi Qin Gao, Zijian Guo, Zhibo Liu

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Abstract

Pt(II) drugs are a widely used chemotherapeutic, yet their side effects can be severe. Here we show that the radiation-induced reduction of Pt(IV) complexes to cytotoxic Pt(II) drugs is rapid, efficient and applicable in water, that it is mediated by hydrated electrons from water radiolysis and that the X-ray-induced release of Pt(II) drugs from an oxaliplatin prodrug in tumours inhibits their growth, as we show with nearly complete tumour regression in mice with subcutaneous human tumour xenografts. The combination of low-dose radiotherapy with a Pt(IV)-based antibody–trastuzumab conjugate led to the tumour-selective release of the chemotherapeutic in mice and to substantial therapeutic benefits. The radiation-induced local reduction of platinum prodrugs in the reductive tumour microenvironment may expand the utility of radiotherapy. Platinum-based chemotherapeutics can be locally released in tumours by leveraging the radiation-induced reduction of platinum prodrugs.

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放疗引发的肿瘤中铂类化疗原药的减少。

铂(II)药物是一种广泛使用的化疗药物，但其副作用也很严重。在这里，我们展示了辐射诱导的铂(IV)复合物还原成细胞毒性铂(II)药物的过程是快速、高效且适用于水的，它是由水辐射分解产生的水合电子介导的，X射线诱导的铂(II)药物从肿瘤中的奥沙利铂原药中释放出来，抑制了肿瘤的生长，正如我们在皮下人类肿瘤异种移植物小鼠身上所展示的那样，肿瘤几乎完全消退。低剂量放疗与基于铂（IV）的抗体-曲妥珠单抗共轭物相结合，可在小鼠体内实现肿瘤选择性释放化疗药物，并带来显著的治疗效果。铂原药在还原性肿瘤微环境中的辐射诱导局部减少可能会扩大放疗的效用。

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 Biomedical Engineering Medicine-Medicine (miscellaneous)

CiteScore

45.30

自引率

1.10%

发文量

138

期刊介绍： Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.