Co-Delivery of Oxaliplatin and Demethylcantharidin via a Polymer-Drug Conjugate

被引：18

作者：

Wang, Enhui ^{[1
]}

Xiong, Hejian ^{[2
,3
]}

Zhou, Dongfang ^{[2
]}

Xie, Zhigang ^{[2
]}

Huang, Yubin ^{[2
]}

Jing, Xiabin ^{[2
]}

Sun, Xinhua ^{[1
]}

机构：

[1] Jilin Univ, Fac Stomatol, Dept Orthodont, Changchun 130021, Peoples R China

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

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

来源：

MACROMOLECULAR BIOSCIENCE | 2014年 / 14卷 / 04期

基金：

中国国家自然科学基金;

关键词：

co-delivery; combination chemotherapy; oxaliplatin; polymer-drug conjugate; PP2A inhibition; TARGETED DELIVERY; CANCER CELLS; COMBINATION; CISPLATIN; PRODRUG; FLUOROURACIL; CHEMOTHERAPY; CANTHARIDIN; LEUCOVORIN; PACLITAXEL;

D O I：

10.1002/mabi.201300402

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A Pt (IV) complex which combined the bioactivities of both oxaliplatin and demethylcantharidin (DMC) is synthesized and delivered by a polymer-drug conjugate for combination chemotherapy. Oxaliplatin is released from the polymer-drug conjugate within cancer cell by reduction to attack nuclear DNA, while a dose of DMC is also hydrolyzed subsequently to block DNA damage-induced defense mechanisms by serine/threonine phosphatase 2A (PP2A) inhibition. In vitro evaluation shows that the polymer-drug conjugate with dual modes of action upon cancer cells displays higher cytotoxicity against SKOV-3 cells than that of free drugs. This enhanced cytotoxicity is attributed to the synergistic effect between oxaliplatin and DMC, as well as the effective intracellular internalization of the micelles observed by confocal laser scanning microscopy (CLSM) imaging.

引用

页码：588 / 596

页数：9

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