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Macromol Biosci. 2013 May;13(5):584-94. doi: 10.1002/mabi.201200441. Epub 2013 Feb 18.

Co-delivery of 10-hydroxycamptothecin with doxorubicin conjugated prodrugs for enhanced anticancer efficacy.

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1
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

Abstract

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.

PMID:
23420692
DOI:
10.1002/mabi.201200441
[Indexed for MEDLINE]
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