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Spatiotemporally Targeted Polypeptide Nanoantidotes Improve Chemotherapy Tolerance of Cisplatin

The toxicity of drugs causes various adverse effects in patients. While antidotes that neutralize drug toxicity help reduce systemic damage during clinical therapy, these antidotes are generally accompanied by the loss of drug efficacy. Herein, the spatiotemporally targeted polycystine‐based nanoant...

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Bibliographic Details
Published in:Angewandte Chemie 2022-11, Vol.134 (47), p.n/a
Main Authors: Yang, Jiazhen, Su, Tianqi, Zou, Haoyang, Yang, Guanqing, Ding, Jianxun, Chen, Xuesi
Format: Article
Language:English
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Summary:The toxicity of drugs causes various adverse effects in patients. While antidotes that neutralize drug toxicity help reduce systemic damage during clinical therapy, these antidotes are generally accompanied by the loss of drug efficacy. Herein, the spatiotemporally targeted polycystine‐based nanoantidotes were designed as a neutralizer of cisplatin (CDDP) to decrease its toxicity without affecting its anticancer efficacy. The nanoantidotes administered before CDDP selectively accumulated in the liver and kidney and then firmly bound to CDDP through the highly stable Pt−S bond during subsequent chemotherapy. This two‐step administration strategy reduced the level of Pt in normal organs, shortened the half‐life of CDDP in plasma, and increased the tolerance to CDDP. More importantly, the nanoantidotes maintained the anticancer efficacy of CDDP after reducing systemic toxicity, indicating its great potential in expanding the clinical application of CDDP. Thanks to the presence of disulfide bonds, nanoantidotes capture cisplatin (CDDP) through highly stable Pt−S bonds to form a series of non‐toxic mononuclear/dinuclear complexes centered on Pt atoms. The pre‐enriched nanoantidotes accelerate the metabolism of CDDP from normal organs, reduce the side effects of chemotherapy, and improve the therapeutic window of the free drug.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202211136