The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals

Ying Men*, Xiao-Xing Wang*, Ruo-Jing Li, Yan Zhang, Wei Tian, Hong-Juan Yao, Rui-Jun Ju, Xue Ying, Jia Zhou, Nan Li, Liang Zhang, Yang Yu, Wan-Liang LuState Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, People&#39;s Republi...

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Autores principales:	Men Y, Wang XX, Li RJ, Zhang Y, Tian W, Yao HJ, Ju RJ, Ying X, Zhou J, Li N,&nbsp;Zhang L, Yu Y,&nbsp;Lu WL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d47b1eb4aa9d4aae80cc093d6af027d9
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spelling	oai:doaj.org-article:d47b1eb4aa9d4aae80cc093d6af027d92021-12-02T05:08:48ZThe efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals1176-91141178-2013https://doaj.org/article/d47b1eb4aa9d4aae80cc093d6af027d92011-12-01T00:00:00Zhttp://www.dovepress.com/the-efficacy-of-mitochondrial-targeting-antiresistant-epirubicin-lipos-a8784https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ying Men, Xiao-Xing Wang, Ruo-Jing Li, Yan Zhang, Wei Tian, Hong-Juan Yao, Rui-Jun Ju, Xue Ying, Jia Zhou, Nan Li, Liang Zhang, Yang Yu, Wan-Liang LuState Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, People&#39;s Republic of China*These authors contributed equally to this manuscriptBackground: Multidrug resistance (MDR) of cancers can be circumvented by inducing programmed cell death, which is known as apoptosis. Mitochondria play a crucial role in apoptosis. Mitochondria-specific therapy would provide an efficient strategy for treating resistant cancers.Design and methods: A strategy was proposed here to overcome MDR by designing cancer mitochondria-specific drug-loaded liposomes, namely, antiresistant epirubicin mitosomes, aimed at treating resistant leukemia by targeting mitochondria. Evaluations were performed on human chronic leukemia K562, MDR K562/ADR cells, and female BALB/c nude mice xenografted with MDR K562/ADR cells. The liposomes were characterized through assays of cytotoxicity, mitochondrial targeting, caspase-9 and caspase-3, antitumor activities, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) analysis.Results: The average size of antiresistant epirubicin mitosomes was in the range of 105&ndash;115 nm. Antiresistant epirubicin mitosomes were effective in inhibiting proliferation of MDR K562/ADR cells in vitro and selectively accumulated into the mitochondria. Caspase-9 and caspase-3 activity was increased after applying antiresistant epirubicin mitosomes. In xenografted resistant MDR K562/ADR tumor in nude mice, antiresistant tumor effect of antiresistant epirubicin mitosomes was evidently observed. Apoptotic inducing effects by antiresistant epirubicin mitosomes were noticeably evidenced via mitochondrial pathway.Conclusions: Antiresistant epirubicin mitosomes had significant inhibitory effect against resistant leukemia in vitro and in vivo, hence providing a promising strategy for improving therapeutic efficacy in resistant human leukemia.Keywords: mitosomes, mitochondria signaling pathway, nude miceMen YWang XXLi RJZhang YTian WYao HJJu RJYing XZhou JLi N,&nbsp;Zhang LYu Y,&nbsp;Lu WLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 3125-3137 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Men Y Wang XX Li RJ Zhang Y Tian W Yao HJ Ju RJ Ying X Zhou J Li N,&nbsp;Zhang L Yu Y,&nbsp;Lu WL The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals
description	Ying Men, Xiao-Xing Wang, Ruo-Jing Li, Yan Zhang, Wei Tian, Hong-Juan Yao, Rui-Jun Ju, Xue Ying, Jia Zhou, Nan Li, Liang Zhang, Yang Yu, Wan-Liang LuState Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, People&#39;s Republic of China*These authors contributed equally to this manuscriptBackground: Multidrug resistance (MDR) of cancers can be circumvented by inducing programmed cell death, which is known as apoptosis. Mitochondria play a crucial role in apoptosis. Mitochondria-specific therapy would provide an efficient strategy for treating resistant cancers.Design and methods: A strategy was proposed here to overcome MDR by designing cancer mitochondria-specific drug-loaded liposomes, namely, antiresistant epirubicin mitosomes, aimed at treating resistant leukemia by targeting mitochondria. Evaluations were performed on human chronic leukemia K562, MDR K562/ADR cells, and female BALB/c nude mice xenografted with MDR K562/ADR cells. The liposomes were characterized through assays of cytotoxicity, mitochondrial targeting, caspase-9 and caspase-3, antitumor activities, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) analysis.Results: The average size of antiresistant epirubicin mitosomes was in the range of 105&ndash;115 nm. Antiresistant epirubicin mitosomes were effective in inhibiting proliferation of MDR K562/ADR cells in vitro and selectively accumulated into the mitochondria. Caspase-9 and caspase-3 activity was increased after applying antiresistant epirubicin mitosomes. In xenografted resistant MDR K562/ADR tumor in nude mice, antiresistant tumor effect of antiresistant epirubicin mitosomes was evidently observed. Apoptotic inducing effects by antiresistant epirubicin mitosomes were noticeably evidenced via mitochondrial pathway.Conclusions: Antiresistant epirubicin mitosomes had significant inhibitory effect against resistant leukemia in vitro and in vivo, hence providing a promising strategy for improving therapeutic efficacy in resistant human leukemia.Keywords: mitosomes, mitochondria signaling pathway, nude mice
format	article
author	Men Y Wang XX Li RJ Zhang Y Tian W Yao HJ Ju RJ Ying X Zhou J Li N,&nbsp;Zhang L Yu Y,&nbsp;Lu WL
author_facet	Men Y Wang XX Li RJ Zhang Y Tian W Yao HJ Ju RJ Ying X Zhou J Li N,&nbsp;Zhang L Yu Y,&nbsp;Lu WL
author_sort	Men Y
title	The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals
title_short	The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals
title_full	The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals
title_fullStr	The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals
title_full_unstemmed	The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals
title_sort	efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/d47b1eb4aa9d4aae80cc093d6af027d9
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The efficacy of mitochondrial targeting antiresistant epirubicin liposomes in treating resistant leukemia in animals

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