The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer

The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer

Lei Liu, Li-Min Mu, Yan Yan, Jia-Shuan Wu, Ying-Jie Hu, Ying-Zi Bu, Jing-Ying Zhang, Rui Liu, Xue-Qi Li, Wan-Liang Lu Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Be...

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Autores principales: Liu L, Mu LM, Yan Y, Wu JS, Hu YJ, Bu YZ, Zhang JY, Liu R, Li XQ, Lu WL
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
Materias:
Mitochondria
drug delivery
apoptosis
efficacy
refractory breast cancer.
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/6ffa3316fd20403a95fbf0055f3ed66b
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spelling oai:doaj.org-article:6ffa3316fd20403a95fbf0055f3ed66b2021-12-02T00:59:55ZThe use of functional epirubicin liposomes to induce programmed death in refractory breast cancer1178-2013https://doaj.org/article/6ffa3316fd20403a95fbf0055f3ed66b2017-06-01T00:00:00Zhttps://www.dovepress.com/the-use-of-functional-epirubicin-liposomes-to-induce-programmed-death--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lei Liu, Li-Min Mu, Yan Yan, Jia-Shuan Wu, Ying-Jie Hu, Ying-Zi Bu, Jing-Ying Zhang, Rui Liu, Xue-Qi Li, Wan-Liang Lu Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China Abstract: Currently, chemotherapy is less efficient in controlling the continued development of breast cancer because it cannot eliminate extrinsic and intrinsic refractory cancers. In this study, mitochondria were modified by functional epirubicin liposomes to eliminate refractory cancers through initiation of an apoptosis cascade. The efficacy and mechanism of epirubicin liposomes were investigated on human breast cancer cells in vitro and in vivo using flow cytometry, confocal microscopy, high-content screening system, in vivo imaging system, and tumor inhibition in mice. Mechanistic studies revealed that the liposomes could target the mitochondria, activate the apoptotic enzymes caspase 8, 9, and 3, upregulate the proapoptotic protein Bax while downregulating the antiapoptotic protein Mcl-1, and induce the generation of reactive oxygen species (ROS) through an apoptosis cascade. In xenografted mice bearing breast cancer, the epirubicin liposomes demonstrated prolonged blood circulation, significantly increased accumulation in tumor tissue, and robust anticancer efficacy. This study demonstrated that functional epirubicin liposomes could significantly induce programmed death of refractory breast cancer by activating caspases and ROS-related apoptotic signaling pathways, in addition to the direct killing effect of the anticancer drug itself. Thus, we present a simple nanomedicine strategy to treat refractory breast cancer. Keywords: mitochondria, drug delivery, apoptosis, efficacy, signaling pathwayLiu LMu LMYan YWu JSHu YJBu YZZhang JYLiu RLi XQLu WLDove Medical PressarticleMitochondriadrug deliveryapoptosisefficacyrefractory breast cancer.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4163-4176 (2017)
institution DOAJ
collection DOAJ
language EN
topic Mitochondria
drug delivery
apoptosis
efficacy
refractory breast cancer.
Medicine (General)
R5-920
spellingShingle Mitochondria
drug delivery
apoptosis
efficacy
refractory breast cancer.
Medicine (General)
R5-920
Liu L
Mu LM
Yan Y
Wu JS
Hu YJ
Bu YZ
Zhang JY
Liu R
Li XQ
Lu WL
The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer
description Lei Liu, Li-Min Mu, Yan Yan, Jia-Shuan Wu, Ying-Jie Hu, Ying-Zi Bu, Jing-Ying Zhang, Rui Liu, Xue-Qi Li, Wan-Liang Lu Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China Abstract: Currently, chemotherapy is less efficient in controlling the continued development of breast cancer because it cannot eliminate extrinsic and intrinsic refractory cancers. In this study, mitochondria were modified by functional epirubicin liposomes to eliminate refractory cancers through initiation of an apoptosis cascade. The efficacy and mechanism of epirubicin liposomes were investigated on human breast cancer cells in vitro and in vivo using flow cytometry, confocal microscopy, high-content screening system, in vivo imaging system, and tumor inhibition in mice. Mechanistic studies revealed that the liposomes could target the mitochondria, activate the apoptotic enzymes caspase 8, 9, and 3, upregulate the proapoptotic protein Bax while downregulating the antiapoptotic protein Mcl-1, and induce the generation of reactive oxygen species (ROS) through an apoptosis cascade. In xenografted mice bearing breast cancer, the epirubicin liposomes demonstrated prolonged blood circulation, significantly increased accumulation in tumor tissue, and robust anticancer efficacy. This study demonstrated that functional epirubicin liposomes could significantly induce programmed death of refractory breast cancer by activating caspases and ROS-related apoptotic signaling pathways, in addition to the direct killing effect of the anticancer drug itself. Thus, we present a simple nanomedicine strategy to treat refractory breast cancer. Keywords: mitochondria, drug delivery, apoptosis, efficacy, signaling pathway
format article
author Liu L
Mu LM
Yan Y
Wu JS
Hu YJ
Bu YZ
Zhang JY
Liu R
Li XQ
Lu WL
author_facet Liu L
Mu LM
Yan Y
Wu JS
Hu YJ
Bu YZ
Zhang JY
Liu R
Li XQ
Lu WL
author_sort Liu L
title The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer
title_short The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer
title_full The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer
title_fullStr The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer
title_full_unstemmed The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer
title_sort use of functional epirubicin liposomes to induce programmed death in refractory breast cancer
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/6ffa3316fd20403a95fbf0055f3ed66b
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