Synergy effects of copper ion in doxorubicin-based chelate prodrug for cancer chemo-chemodynamic combination therapy

被引：4

作者：

Zhang, Wen ^{[1
]}

Zhang, Peng ^{[1
,2
]}

Xu, Xiaopeng ^{[1
]}

Li, Minghui ^{[1
]}

Wang, Shasha ^{[1
]}

Mu, Hongjie ^{[1
]}

Sun, Kaoxiang ^{[1
,2
]}

机构：

[1] Yantai Univ, Collaborat Innovat Ctr Adv Drug Delivery Syst & Bi, Minist Educ, Sch Pharm,Key Lab Mol Pharmacol & Drug Evaluat, Yantai, Peoples R China

[2] Yantai Univ, Sch Pharm, 30 Qingquan Rd, Yantai 264005, Shandong, Peoples R China

来源：

DRUG DELIVERY | 2023年 / 30卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Chemodynamic therapy; chemotherapy; combination therapy; cytotoxicity; antitumor; safety; EFFICACY;

D O I：

10.1080/10717544.2023.2219426

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Doxorubicin (DOX) is a commonly studied chemotherapeutic agent for the treatment of solid tumors, but the severe side effects limit its clinical application. It is shown that DOX-metal chelate has lower in vitro cytotoxicity compared with DOX, as the anthracyclines of DOX can form coordinative interaction with transition metal ions. In addition, the transition metal ions could catalyze the production of hydroxyl radicals (center dot OH) via Fenton/Fenton-like reactions to achieve antitumor chemodynamic therapy (CDT). In this study, copper ions (Cu2+) were applied to obtain DOX/Cu(II) prodrug, and a liposomal formulation was used to avoid the rapid blood clearance and optimize the biodistribution of this prodrug. In vitro and in vivo antitumor results demonstrated that this pH sensitive Cu-chelating prodrug can reduce adverse effects of DOX but improve the antitumor efficiency due to the combination of chemotherapy and chemodynamic therapy. Our study provided a facile and effective approach of metal-chelating prodrug strategy for combination cancer therapy strategy.

引用

页数：14