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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doaj-95927b665b064f3684cbd8e19d1989cb2020-11-24T22:15:23ZengDove Medical PressInternational Journal of Nanomedicine1178-20132018-02-01Volume 1371973136660Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administrationDian LHHu YJLin JYZhang JYYan YCui YNSu ZBLu WLLing-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, micehttps://www.dovepress.com/fabrication-of-paclitaxel-hybrid-nanomicelles-to-treat-resistant-breas-peer-reviewed-article-IJNPaclitaxelnanomicellesoraldrug resistant breast cancermice. |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dian LH Hu YJ Lin JY Zhang JY Yan Y Cui YN Su ZB Lu WL |
spellingShingle |
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 International Journal of Nanomedicine Paclitaxel nanomicelles oral drug resistant breast cancer mice. |
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 |
series |
International Journal of Nanomedicine |
issn |
1178-2013 |
publishDate |
2018-02-01 |
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 |
topic |
Paclitaxel nanomicelles oral drug resistant breast cancer mice. |
url |
https://www.dovepress.com/fabrication-of-paclitaxel-hybrid-nanomicelles-to-treat-resistant-breas-peer-reviewed-article-IJN |
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