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

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, Ningb...

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Autores principales:	Zhu CY, Xiao JJ, Tang M, Feng H, Chen WL, Du M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	dual drugs co-delivery system amphiphilic diblock copolymer shell cross-linking micelles synergistic combination cancer therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fe464a9442bb438aba7609ee564c515e
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spelling	oai:doaj.org-article:fe464a9442bb438aba7609ee564c515e2021-12-02T07:36:51ZPlatinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy1178-2013https://doaj.org/article/fe464a9442bb438aba7609ee564c515e2017-05-01T00:00:00Zhttps://www.dovepress.com/platinum-covalent-shell-cross-linked-micelles-designed-to-deliver-doxo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Caiying 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 therapyZhu CYXiao JJTang MFeng HChen WLDu MDove Medical Pressarticledual drugs co-delivery systemamphiphilic diblock copolymershell cross-linking micellessynergistic combination cancer therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3697-3710 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	dual drugs co-delivery system amphiphilic diblock copolymer shell cross-linking micelles synergistic combination cancer therapy Medicine (General) R5-920
spellingShingle	dual drugs co-delivery system amphiphilic diblock copolymer shell cross-linking micelles synergistic combination cancer therapy Medicine (General) R5-920 Zhu CY Xiao JJ Tang M Feng H Chen WL Du M Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy
description	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
format	article
author	Zhu CY Xiao JJ Tang M Feng H Chen WL Du M
author_facet	Zhu CY Xiao JJ Tang M Feng H Chen WL Du M
author_sort	Zhu CY
title	Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy
title_short	Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy
title_full	Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy
title_fullStr	Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy
title_full_unstemmed	Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy
title_sort	platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/fe464a9442bb438aba7609ee564c515e
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Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy

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