Spatiotemporally Targeted Polypeptide Nanoantidotes Improve Chemotherapy Tolerance of Cisplatin

作者：Jia-Zhen Yang, Tianqi Su, Haoyang Zou, Guanqing Yang, Jianxun Ding, Xuesi Chen · 发表于：Angewandte Chemie International Edition · 年份：2022 · DOI：10.1002/anie.202211136 · 被引用次数：39 · 研究领域：Nanoparticle-Based Drug Delivery、Nanocluster Synthesis and Applications、Advanced biosensing and bioanalysis techniques

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.