Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

Yunfang Zhou,1,* Shuanghu Wang,1,* Xuhua Ying,2 Yifan Wang,2 Peiwu Geng,1 Aiping Deng,3 Zhihong Yu3 1The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, 2Cancer Institute of Integrative Medicine, Zhejia...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhou YF, Wang SH, Ying XH, Wang YF, Geng PW, Deng AP, Yu ZH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	multidrug resistance doxorubicin indomethacin redox-responsive micelles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/daeb37c106d14fc8985a0ef842483725
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:daeb37c106d14fc8985a0ef842483725
record_format	dspace
spelling	oai:doaj.org-article:daeb37c106d14fc8985a0ef8424837252021-12-02T05:40:37ZDoxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer1178-2013https://doaj.org/article/daeb37c106d14fc8985a0ef8424837252017-08-01T00:00:00Zhttps://www.dovepress.com/doxorubicin-loaded-redox-responsive-micelles-based-on-dextran-and-indo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yunfang Zhou,1,* Shuanghu Wang,1,* Xuhua Ying,2 Yifan Wang,2 Peiwu Geng,1 Aiping Deng,3 Zhihong Yu3 1The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, 2Cancer Institute of Integrative Medicine, Zhejiang Academy of Chinese Medicine, Hangzhou, 3Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China *These authors contributed equally to this work Abstract: Multidrug resistance (MDR) against chemotherapeutic agents has become one of the major obstacles to successful cancer therapy and MDR-associated proteins (MRPs)-mediated drug efflux is the key factor for MDR. In this study, a redox-responsive polymer based on dextran (DEX) and indomethacin (IND), which could reduce MRPs-mediated efflux of chemotherapeutics, was synthesized, and the obtained polymer could spontaneously form stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 50 nm and effectively encapsulate doxorubicin (DOX); the micelles contain a disulfide bridge (cystamine, SS) between IND and DEX (DEX-SS-IND). In vitro drug release results indicated that DEX-SS-IND/DOX micelles could maintain good stability in a stimulated normal physiological environment and promptly depolymerized and released DOX in a reducing environment. After incubating DEX-SS-IND/DOX micelles with drug-resistant tumor (MCF-7/ADR) cells, the intracellular accumulation and retention of DOX were significantly increased under the synergistic effects of redox-responsive delivery and the inhibitory effect of IND on MRPs. In vitro cytotoxicity showed that DEX-SS-IND/DOX micelles exhibited higher cytotoxicity against MCF-7/ADR cells. Moreover, DEX-SS-IND/DOX micelles showed significantly enhanced inhibition of tumor in BALB/c nude mice bearing MCF-7/ADR tumors and reduced systemic toxicity. Overall, the cumulative evidence indicates that DEX-SS-IND/DOX micelles hold significant promise for overcoming MDR for cancer therapy. Keywords: multidrug resistance, doxorubicin, indomethacin, redox-responsive, micelles, breast cancerZhou YFWang SHYing XHWang YFGeng PWDeng APYu ZHDove Medical Pressarticlemultidrug resistancedoxorubicinindomethacinredox-responsivemicellesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6153-6168 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	multidrug resistance doxorubicin indomethacin redox-responsive micelles Medicine (General) R5-920
spellingShingle	multidrug resistance doxorubicin indomethacin redox-responsive micelles Medicine (General) R5-920 Zhou YF Wang SH Ying XH Wang YF Geng PW Deng AP Yu ZH Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer
description	Yunfang Zhou,1,* Shuanghu Wang,1,* Xuhua Ying,2 Yifan Wang,2 Peiwu Geng,1 Aiping Deng,3 Zhihong Yu3 1The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, 2Cancer Institute of Integrative Medicine, Zhejiang Academy of Chinese Medicine, Hangzhou, 3Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China *These authors contributed equally to this work Abstract: Multidrug resistance (MDR) against chemotherapeutic agents has become one of the major obstacles to successful cancer therapy and MDR-associated proteins (MRPs)-mediated drug efflux is the key factor for MDR. In this study, a redox-responsive polymer based on dextran (DEX) and indomethacin (IND), which could reduce MRPs-mediated efflux of chemotherapeutics, was synthesized, and the obtained polymer could spontaneously form stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of 50 nm and effectively encapsulate doxorubicin (DOX); the micelles contain a disulfide bridge (cystamine, SS) between IND and DEX (DEX-SS-IND). In vitro drug release results indicated that DEX-SS-IND/DOX micelles could maintain good stability in a stimulated normal physiological environment and promptly depolymerized and released DOX in a reducing environment. After incubating DEX-SS-IND/DOX micelles with drug-resistant tumor (MCF-7/ADR) cells, the intracellular accumulation and retention of DOX were significantly increased under the synergistic effects of redox-responsive delivery and the inhibitory effect of IND on MRPs. In vitro cytotoxicity showed that DEX-SS-IND/DOX micelles exhibited higher cytotoxicity against MCF-7/ADR cells. Moreover, DEX-SS-IND/DOX micelles showed significantly enhanced inhibition of tumor in BALB/c nude mice bearing MCF-7/ADR tumors and reduced systemic toxicity. Overall, the cumulative evidence indicates that DEX-SS-IND/DOX micelles hold significant promise for overcoming MDR for cancer therapy. Keywords: multidrug resistance, doxorubicin, indomethacin, redox-responsive, micelles, breast cancer
format	article
author	Zhou YF Wang SH Ying XH Wang YF Geng PW Deng AP Yu ZH
author_facet	Zhou YF Wang SH Ying XH Wang YF Geng PW Deng AP Yu ZH
author_sort	Zhou YF
title	Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer
title_short	Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer
title_full	Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer
title_fullStr	Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer
title_full_unstemmed	Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer
title_sort	doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/daeb37c106d14fc8985a0ef842483725
work_keys_str_mv	AT zhouyf doxorubicinloadedredoxresponsivemicellesbasedondextranandindomethacinforresistantbreastcancer AT wangsh doxorubicinloadedredoxresponsivemicellesbasedondextranandindomethacinforresistantbreastcancer AT yingxh doxorubicinloadedredoxresponsivemicellesbasedondextranandindomethacinforresistantbreastcancer AT wangyf doxorubicinloadedredoxresponsivemicellesbasedondextranandindomethacinforresistantbreastcancer AT gengpw doxorubicinloadedredoxresponsivemicellesbasedondextranandindomethacinforresistantbreastcancer AT dengap doxorubicinloadedredoxresponsivemicellesbasedondextranandindomethacinforresistantbreastcancer AT yuzh doxorubicinloadedredoxresponsivemicellesbasedondextranandindomethacinforresistantbreastcancer
_version_	1718400324869292032

Doxorubicin-loaded redox-responsive micelles based on dextran and indomethacin for resistant breast cancer

Ejemplares similares