Preparation and anticancer actions of CuET-nanoparticles dispersed by bovine serum albumin

文献类型： 外文期刊

第一作者： He, Yufeng

作者： He, Yufeng;Yang, Mingchuan;Yang, Lumin;Hao, Meng;Wang, Fuming;Li, Xiuli;Zhang, Jinsong;He, Yufeng;Zhang, Xiangchun;Taylor, Ethan Will

作者机构：

关键词： Diethyldithiocarbamate; Copper; Nanoparticles; Hydroxyl radicals; Glutathione

期刊名称：COLLOIDS AND SURFACES B-BIOINTERFACES （ 影响因子：5.8； 五年影响因子：5.4 ）

ISSN： 0927-7765

年卷期： 2023 年 226 卷

页码：

收录情况： SCI

摘要： Diethyldithiocarbamate-copper complex (CuET) shows promising anticancer effect; nonetheless, preclinical evaluations of CuET are hindered due to poor solubility. We prepared bovine serum albumin (BSA)-dispersed CuET nanoparticles (CuET-NPs) to overcome the shortcoming. Results from a cell-free redox system demonstrated that CuET-NPs reacted with glutathione, leading to form hydroxyl radical. Glutathione-mediated production of hydroxyl radicals may help explain why CuET selectively kills drug-resistant cancer cells with higher levels of glutathione. CuET-NPs dispersed by autoxidation products of green tea epigallocatechin gallate (EGCG) also reacted with glutathione; however, the autoxidation products eradicated hydroxyl radicals; consequently, such CuET-NPs exhibited largely compromised cytotoxicity, suggesting that hydroxyl radical is a crucial mediator of CuET anticancer activity. In cancer cells, BSA-dispersed CuET-NPs exhibited cytotoxic activities equivalent to CuET and induced protein poly-ubiquitination. Moreover, the reported powerful inhibition of CuET on colony formation and migration of cancer cells could be replicated by CuET-NPs. These similarities demonstrate BSA-dispersed CuET-NPs is identical to CuET. Thus, we advanced to pilot toxicological and pharmacological evaluations. CuET-NPs caused hematologic toxicities in mice and induced protein poly-ubiquitination and apoptosis of cancer cells inoculated in mice at a defined pharmacological dose. Given high interest in CuET and its poor solubility, BSA-dispersed CuET-NPs pave the way for preclinical evaluations.

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