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Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy

Authors Zhu CY, Xiao JJ, Tang M, Feng H, Chen WL, Du M

Received 22 December 2016

Accepted for publication 18 April 2017

Published 12 May 2017 Volume 2017:12 Pages 3697—3710

DOI https://doi.org/10.2147/IJN.S130938

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Caiying Zhu,1,* Jingjing Xiao,1,* Ming Tang,2 Hua Feng,1 Wulian Chen,3 Ming Du1

1Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital, Shanghai Medical College, Fudan University, Shanghai, 2Department of Otorhinolaryngology-Head and Neck Surgery, Ningbo Medical Center, Li Huli Hospital, Ningbo, 3State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, China

*These authors contributed equally to this work

Abstract: The preparation of polymer therapeutics capable of controlled release of multiple chemotherapeutic drugs has remained a tough problem in synergistic combination cancer therapy. Herein, a novel dual-drug co-delivery system carrying doxorubicin (DOX) and platinum(IV) (Pt[IV]) was developed. An amphiphilic diblock copolymer, PCL-b-P(OEGMA-co-AzPMA), was synthesized and used as a nanoscale drug carrier in which DOX and Pt(IV) could be packaged together. The copolymers were shell cross-linked by Pt(IV) prodrug via a click reaction. Studies on the in vitro drug release and cellular uptake of the dual-drug co-delivery system showed that the micelles were effectively taken up by the cells and simultaneously released drugs in the cells. Futhermore, the co-delivery polymer nanoparticles caused much higher cell death in HeLa and A357 tumor cells than either the free drugs or single-drug-loaded micelles at the same dosage, exhibiting a synergistic combination of DOX and Pt(IV). The results obtained with the shell cross-linked micelles based on an anticancer drug used as a cross-linking linkage suggested a promising application of the micelles for multidrug delivery in combination cancer therapy.

Keywords: dual-drug co-delivery system, amphiphilic diblock copolymer, shell cross-linked micelles, synergistic combination cancer therapy

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