Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration

Ling-Hui Dian,1,2,* Ying-Jie Hu,1,* Jia-Ye Lin,1 Jing-Ying Zhang,1 Yan Yan,1 Yi-Nuo Cui,1 Zhan-Bo Su,1 Wan-Liang Lu1 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Pharmaceutical Sciences, Guangdong Medical University...

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Autores principales:	Dian LH, Hu YJ, Lin JY, Zhang JY, Yan Y, Cui YN, Su ZB, Lu WL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Paclitaxel nanomicelles oral drug resistant breast cancer mice. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/95927b665b064f3684cbd8e19d1989cb
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spelling	oai:doaj.org-article:95927b665b064f3684cbd8e19d1989cb2021-12-02T02:34:27ZFabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration1178-2013https://doaj.org/article/95927b665b064f3684cbd8e19d1989cb2018-02-01T00:00:00Zhttps://www.dovepress.com/fabrication-of-paclitaxel-hybrid-nanomicelles-to-treat-resistant-breas-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ling-Hui Dian,1,2,* Ying-Jie Hu,1,* Jia-Ye Lin,1 Jing-Ying Zhang,1 Yan Yan,1 Yi-Nuo Cui,1 Zhan-Bo Su,1 Wan-Liang Lu1 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Pharmaceutical Sciences, Guangdong Medical University, Dongguan, China *These authors contributed equally to this work Aim: Oral chemotherapy using anticancer drugs would improve the clinical practice and the life quality of patients. The aim of the present study was to develop paclitaxel hybrid nanomicelles for oral administration to treat resistant breast cancer. Methods: Evaluations were performed on human breast cancer MCF-7 cells, drug-resistant breast cancer MCF-7/Adr cells, and in MCF-7/Adr-xenografted BALB/c nude mice. The nanomicelles were composed of the polymer soluplus, d-α-tocopheryl polyethyleneglycol 1000 succinate (TPGS1000), and dequalinium (DQA). The constructed paclitaxel hybrid nanomicelles were ~65 nm in size. Results: The nanomicelles improved cellular uptake and anticancer efficacy in the resistant breast cancer cells and induced mitochondria-mediated apoptosis. The mechanism of the apoptosis-inducing effect was related to the co-localization of the nanomicelles with mitochondria; the activation of pro-apoptotic protein Bax, cytochrome C, and apoptotic enzymes caspase 9 and 3; and the inhibition of anti-apoptotic proteins Bcl-2 and Mcl-1. Oral administration of paclitaxel hybrid nanomicelles had the same anticancer efficacy as the intravenous injection of taxol in resistant breast cancer-bearing mice. The oral suitability of this formulation was associated with the nanostructure and the actions of TPGS1000 and DQA. Conclusion: The fabricated paclitaxel hybrid nanomicelles could provide a promising oral formulation to treat drug-resistant breast cancer. Keywords: paclitaxel, nanomicelles, oral, drug-resistant breast cancer, miceDian LHHu YJLin JYZhang JYYan YCui YNSu ZBLu WLDove Medical PressarticlePaclitaxelnanomicellesoraldrug resistant breast cancermice.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 719-731 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Paclitaxel nanomicelles oral drug resistant breast cancer mice. Medicine (General) R5-920
spellingShingle	Paclitaxel nanomicelles oral drug resistant breast cancer mice. Medicine (General) R5-920 Dian LH Hu YJ Lin JY Zhang JY Yan Y Cui YN Su ZB Lu WL Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration
description	Ling-Hui Dian,1,2,* Ying-Jie Hu,1,* Jia-Ye Lin,1 Jing-Ying Zhang,1 Yan Yan,1 Yi-Nuo Cui,1 Zhan-Bo Su,1 Wan-Liang Lu1 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Pharmaceutical Sciences, Guangdong Medical University, Dongguan, China *These authors contributed equally to this work Aim: Oral chemotherapy using anticancer drugs would improve the clinical practice and the life quality of patients. The aim of the present study was to develop paclitaxel hybrid nanomicelles for oral administration to treat resistant breast cancer. Methods: Evaluations were performed on human breast cancer MCF-7 cells, drug-resistant breast cancer MCF-7/Adr cells, and in MCF-7/Adr-xenografted BALB/c nude mice. The nanomicelles were composed of the polymer soluplus, d-α-tocopheryl polyethyleneglycol 1000 succinate (TPGS1000), and dequalinium (DQA). The constructed paclitaxel hybrid nanomicelles were ~65 nm in size. Results: The nanomicelles improved cellular uptake and anticancer efficacy in the resistant breast cancer cells and induced mitochondria-mediated apoptosis. The mechanism of the apoptosis-inducing effect was related to the co-localization of the nanomicelles with mitochondria; the activation of pro-apoptotic protein Bax, cytochrome C, and apoptotic enzymes caspase 9 and 3; and the inhibition of anti-apoptotic proteins Bcl-2 and Mcl-1. Oral administration of paclitaxel hybrid nanomicelles had the same anticancer efficacy as the intravenous injection of taxol in resistant breast cancer-bearing mice. The oral suitability of this formulation was associated with the nanostructure and the actions of TPGS1000 and DQA. Conclusion: The fabricated paclitaxel hybrid nanomicelles could provide a promising oral formulation to treat drug-resistant breast cancer. Keywords: paclitaxel, nanomicelles, oral, drug-resistant breast cancer, mice
format	article
author	Dian LH Hu YJ Lin JY Zhang JY Yan Y Cui YN Su ZB Lu WL
author_facet	Dian LH Hu YJ Lin JY Zhang JY Yan Y Cui YN Su ZB Lu WL
author_sort	Dian LH
title	Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration
title_short	Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration
title_full	Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration
title_fullStr	Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration
title_full_unstemmed	Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration
title_sort	fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/95927b665b064f3684cbd8e19d1989cb
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Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration

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