Overcoming tumor resistance to cisplatin through micelle-mediated combination chemotherapy

被引：40

作者：

Zhou, Dongfang ^{[1
]}

Cong, Yuwei ^{[1
,2
]}

Qi, Yanxin ^{[1
]}

He, Shasha ^{[1
,2
]}

Xiong, Hejian ^{[1
,2
]}

Wu, Yanjuan ^{[1
,2
]}

Xie, Zhigang ^{[1
]}

Chen, Xuesi ^{[3
]}

Jing, Xiabin ^{[1
]}

Huang, Yubin ^{[1
]}

机构：

[1] Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Chinese Acad Sci, Changchun Inst Appl Chem, Key Lab Polymer Ecomat, Changchun 130022, Peoples R China

来源：

BIOMATERIALS SCIENCE | 2015年 / 3卷 / 01期

基金：

中国国家自然科学基金;

关键词：

PLATINUM RESISTANCE; DNA-REPAIR; DELIVERY; NANOPARTICLES; COMPLEXES; DESIGN; GLUTATHIONE; MITAPLATIN; MECHANISMS; STRATEGIES;

D O I：

10.1039/c4bm00305e

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

The main obstacles to cancer therapy are the inability to target cancer cells and the acquired drug resistance after a period of chemotherapy. Reduced drug uptake and DNA repair are the two main mechanisms involved in cisplatin resistance. In the present investigation, canthaplatin, a Pt(IV) pro-drug of cisplatin and a protein phosphatase 2A (PP2A) inhibitor (4-(3-carboxy-7-oxa-bicyclo[2.2.1]heptane-2-carbonyl)piperazine-1-carboxylic acid tert-butyl ester), was designed and delivered using PEG-b-PLGA micelles for combination chemotherapy. Polymer/canthaplatin micelles facilitated the delivery of the drug into cancer cells through endocytosis and diminished DNA repair by PP2A inhibition, resulting in enhanced anti-tumor efficiency and excellent reversal ability of tumor resistance to cisplatin both in vitro and in vivo. Additionally, the polymer/canthaplatin micelles could prolong drug residence in the blood and decrease the side effects when compared to cisplatin.

引用

页码：182 / 191

页数：10

共 41 条

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