Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer

Fang Bai,1–3,* You Yin,4,* Ting Chen,1,* Jihui Chen,1 Meixin Ge,2 Yunshu Lu,2 Fangyuan Xie,5 Jian Zhang,1 Kejin Wu,3 Yan Liu1,6 1Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of General Surgery, Xinhua Hospital, Affiliated...

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Autores principales:	Bai F, Yin Y, Chen T, Chen J, Ge M, Lu Y, Xie F, Zhang J, Wu K, Liu Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	cancer nanotechnology breast cancer multidrug resistance pemetrexed liposomes Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/88917c80954f46778321f434ab1c44cd
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spelling	oai:doaj.org-article:88917c80954f46778321f434ab1c44cd2021-12-02T02:42:31ZDevelopment of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer1178-2013https://doaj.org/article/88917c80954f46778321f434ab1c44cd2018-03-01T00:00:00Zhttps://www.dovepress.com/development-of-liposomal-pemetrexed-for-enhanced-therapy-against-multi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fang Bai,1–3,* You Yin,4,* Ting Chen,1,* Jihui Chen,1 Meixin Ge,2 Yunshu Lu,2 Fangyuan Xie,5 Jian Zhang,1 Kejin Wu,3 Yan Liu1,6 1Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 3Department of Breast Surgery, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 4Department of Neurology, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, 5Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 6Department of Pharmacy, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Breast cancer is the most common cancer among women. Pemetrexed, a new generation antifolate drug, is one of the primary treatments for breast cancer. However, multidrug resistance (MDR) in breast cancer greatly hampers the therapeutic efficacy of chemotherapies such as pemetrexed. Nanomedicine is emerging as a promising alternative technique to overcome cancer MDR. Thus, pemetrexed-loaded d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) liposomes (liposomal pemetrexed) were developed as a strategy to overcome MDR to pemetrexed in breast cancer. Materials and methods: Liposomal pemetrexed was developed using the calcium acetate gradient method. The cytotoxic effects, apoptosis-inducing activity, in vivo distribution, and antitumor activity of liposomal pemetrexed were investigated. Results: Liposomal pemetrexed was small in size (160.77 nm), with a small polydispersity of <0.1. The encapsulation efficacy of liposomal pemetrexed was 63.5%, which is rather high for water-soluble drugs in liposomes. The IC50 of liposomal pemetrexed following treatment with MDR breast cancer cells (MCF-7 cells overexpressing ABCC5) was 2.6-fold more effective than pemetrexed. The in vivo biodistribution study showed that the liposomes significantly accumulated in tumors 24 h after injection. The antitumor assay in mice bearing MDR breast cancer xenograft tumors confirmed the superior antitumor activity of liposomal pemetrexed over pemetrexed. It was also found that the improved therapeutic effect of liposomal pemetrexed may be attributed to apoptosis through both extrinsic and intrinsic pathways. Conclusion: Liposomal pemetrexed represents a potential therapeutic approach for overcoming breast cancer MDR. Keywords: cancer nanotechnology, breast cancer, multidrug resistance, pemetrexed, liposomesBai FYin YChen TChen JGe MLu YXie FZhang JWu KLiu YDove Medical Pressarticlecancer nanotechnologybreast cancermultidrug resistancepemetrexedliposomesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1327-1339 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer nanotechnology breast cancer multidrug resistance pemetrexed liposomes Medicine (General) R5-920
spellingShingle	cancer nanotechnology breast cancer multidrug resistance pemetrexed liposomes Medicine (General) R5-920 Bai F Yin Y Chen T Chen J Ge M Lu Y Xie F Zhang J Wu K Liu Y Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer
description	Fang Bai,1–3,* You Yin,4,* Ting Chen,1,* Jihui Chen,1 Meixin Ge,2 Yunshu Lu,2 Fangyuan Xie,5 Jian Zhang,1 Kejin Wu,3 Yan Liu1,6 1Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 3Department of Breast Surgery, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 4Department of Neurology, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, 5Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 6Department of Pharmacy, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: Breast cancer is the most common cancer among women. Pemetrexed, a new generation antifolate drug, is one of the primary treatments for breast cancer. However, multidrug resistance (MDR) in breast cancer greatly hampers the therapeutic efficacy of chemotherapies such as pemetrexed. Nanomedicine is emerging as a promising alternative technique to overcome cancer MDR. Thus, pemetrexed-loaded d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) liposomes (liposomal pemetrexed) were developed as a strategy to overcome MDR to pemetrexed in breast cancer. Materials and methods: Liposomal pemetrexed was developed using the calcium acetate gradient method. The cytotoxic effects, apoptosis-inducing activity, in vivo distribution, and antitumor activity of liposomal pemetrexed were investigated. Results: Liposomal pemetrexed was small in size (160.77 nm), with a small polydispersity of <0.1. The encapsulation efficacy of liposomal pemetrexed was 63.5%, which is rather high for water-soluble drugs in liposomes. The IC50 of liposomal pemetrexed following treatment with MDR breast cancer cells (MCF-7 cells overexpressing ABCC5) was 2.6-fold more effective than pemetrexed. The in vivo biodistribution study showed that the liposomes significantly accumulated in tumors 24 h after injection. The antitumor assay in mice bearing MDR breast cancer xenograft tumors confirmed the superior antitumor activity of liposomal pemetrexed over pemetrexed. It was also found that the improved therapeutic effect of liposomal pemetrexed may be attributed to apoptosis through both extrinsic and intrinsic pathways. Conclusion: Liposomal pemetrexed represents a potential therapeutic approach for overcoming breast cancer MDR. Keywords: cancer nanotechnology, breast cancer, multidrug resistance, pemetrexed, liposomes
format	article
author	Bai F Yin Y Chen T Chen J Ge M Lu Y Xie F Zhang J Wu K Liu Y
author_facet	Bai F Yin Y Chen T Chen J Ge M Lu Y Xie F Zhang J Wu K Liu Y
author_sort	Bai F
title	Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer
title_short	Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer
title_full	Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer
title_fullStr	Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer
title_full_unstemmed	Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer
title_sort	development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by abcc5 in breast cancer
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/88917c80954f46778321f434ab1c44cd
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Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer

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