Co-delivery of 10-Hydroxycamptothecin with Doxorubicin Conjugated Prodrugs for Enhanced Anticancer Efficacy

被引:70
作者
Zhang, Yu [1 ,2 ]
Xiao, Chunsheng [1 ]
Li, Mingqiang [1 ,2 ]
Chen, Jie [1 ]
Ding, Jianxun [1 ]
He, Chaoliang [1 ]
Zhuang, Xiuli [1 ]
Chen, Xuesi [1 ]
机构
[1] Chinese Acad Sci, Changchun Inst Appl Chem, Key Lab Polymer Ecomat, Changchun 130022, Peoples R China
[2] Chinese Acad Sci, Grad Univ, Beijing 100039, Peoples R China
基金
中国国家自然科学基金;
关键词
drug delivery systems; nanoparticles; self-assembly; stimuli-sensitive polymers; DRUG-DELIVERY; POLY(ETHYLENE OXIDE); NANOPARTICLES; CAMPTOTHECIN; MICELLES; THERAPY;
D O I
10.1002/mabi.201200441
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
Well-defined amphiphilic linear-dendritic prodrugs (MPEG-b-PAMAM-DOX) are synthesized by conjugating doxorubicin (DOX), to MPEG-b-PAMAM through the acid-labile hydrazone bond. The amphiphilic prodrugs form self-assembled nanoparticles in deionized water and encapsulate the hydrophobic anticancer drug 10-hydroxycamptothecin (HCPT) with a high drug loading efficiency. Studies on drug release and cellular uptake of the co-delivery system reveal that both drugs are released in a pH-dependent manner and effectively taken up by MCF-7 cells. In vitro methyl thiazolyl tetrazolium (MTT) assays and drug-induced apoptosis tests demonstrate the HCPT-loaded nanoparticles suppress cancer cell growth more efficiently than the MPEG-b-PAMAM-DOX prodrugs, free HCPT, and physical mixtures of MPEG-b-PAMAM-DOX and HCPT at equivalent DOX or HCPT doses.
引用
收藏
页码:584 / 594
页数:11
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