Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers

Wenjing Huang,1 Yan Lang,1 Abdul Hakeem,1 Yan Lei,2 Lu Gan,1 Xiangliang Yang1 1Department of Nanomedicine and Biopharmaceuticals, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; 2Pharm...

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Autores principales:	Huang W, Lang Y, Hakeem Abdul, Lei Y, Gan L, Yang X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	cancer multidrug resistance cellular uptake cellular efflux biodistribution Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ccf7c9786edd4f1db21346bfa096b5d0
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spelling	oai:doaj.org-article:ccf7c9786edd4f1db21346bfa096b5d02021-12-02T03:22:59ZSurfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers1178-2013https://doaj.org/article/ccf7c9786edd4f1db21346bfa096b5d02018-03-01T00:00:00Zhttps://www.dovepress.com/surfactin-based-nanoparticles-loaded-with-doxorubicin-to-overcome-mult-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wenjing Huang,1 Yan Lang,1 Abdul Hakeem,1 Yan Lei,2 Lu Gan,1 Xiangliang Yang1 1Department of Nanomedicine and Biopharmaceuticals, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; 2Pharmacy of School Hospital, Huazhong University of Science and Technology, Wuhan 430074, China Background: Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. Developing efficient strategies to reverse MDR remains a major challenge. Surfactin (SUR), a cyclic lipopeptide biosurfactant, has been found to display anticancer activity. Methods: In this paper, SUR was assembled by solvent-emulsion method to load the anticancer drug doxorubicin (DOX). The cytotoxicity of DOX-loaded SUR nanoparticles (DOX@SUR) against DOX-resistant human breast cancer MCF-7/ADR is measured by MTT assay. The cellular uptake and intracellular retention of DOX@SUR are determined by flow cytometry. The tumor accumulation and anticancer activity of DOX@SUR are evaluated in MCF-7/ADR-bearing nude mice. Results: DOX@SUR induce stronger cytotoxicity against DOX-resistant human breast cancer MCF-7/ADR cells compared to free DOX. DOX@SUR nanoparticles exhibit enhanced cellular uptake and decreased cellular efflux, which might be associated with reduced P-glycoprotein expression. After internalization into MCF-7/ADR cells by macropinocytosis- and caveolin-mediated endocytosis, DOX@SUR nanoparticles are colocalized with the lysosomes and translocated to the nucleus to exert cytotoxicity. Furthermore, in vivo animal experiment shows that the DOX@ SUR nanoparticles are accumulated more efficiently in tumors than free DOX. Meanwhile, DOX@SUR nanoparticles display stronger tumor inhibition activity and fewer side effects in MCF-7/ADR-bearing nude mice. Conclusion: This study indicates that SUR-based nanocarrier might present a promising platform to reverse MDR in cancer chemotherapy. Keywords: multidrug resistance, cellular uptake, cellular efflux, biodistributionHuang WLang YHakeem AbdulLei YGan LYang XDove Medical Pressarticlecancermultidrug resistancecellular uptakecellular effluxbiodistributionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1723-1736 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer multidrug resistance cellular uptake cellular efflux biodistribution Medicine (General) R5-920
spellingShingle	cancer multidrug resistance cellular uptake cellular efflux biodistribution Medicine (General) R5-920 Huang W Lang Y Hakeem Abdul Lei Y Gan L Yang X Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers
description	Wenjing Huang,1 Yan Lang,1 Abdul Hakeem,1 Yan Lei,2 Lu Gan,1 Xiangliang Yang1 1Department of Nanomedicine and Biopharmaceuticals, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; 2Pharmacy of School Hospital, Huazhong University of Science and Technology, Wuhan 430074, China Background: Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. Developing efficient strategies to reverse MDR remains a major challenge. Surfactin (SUR), a cyclic lipopeptide biosurfactant, has been found to display anticancer activity. Methods: In this paper, SUR was assembled by solvent-emulsion method to load the anticancer drug doxorubicin (DOX). The cytotoxicity of DOX-loaded SUR nanoparticles (DOX@SUR) against DOX-resistant human breast cancer MCF-7/ADR is measured by MTT assay. The cellular uptake and intracellular retention of DOX@SUR are determined by flow cytometry. The tumor accumulation and anticancer activity of DOX@SUR are evaluated in MCF-7/ADR-bearing nude mice. Results: DOX@SUR induce stronger cytotoxicity against DOX-resistant human breast cancer MCF-7/ADR cells compared to free DOX. DOX@SUR nanoparticles exhibit enhanced cellular uptake and decreased cellular efflux, which might be associated with reduced P-glycoprotein expression. After internalization into MCF-7/ADR cells by macropinocytosis- and caveolin-mediated endocytosis, DOX@SUR nanoparticles are colocalized with the lysosomes and translocated to the nucleus to exert cytotoxicity. Furthermore, in vivo animal experiment shows that the DOX@ SUR nanoparticles are accumulated more efficiently in tumors than free DOX. Meanwhile, DOX@SUR nanoparticles display stronger tumor inhibition activity and fewer side effects in MCF-7/ADR-bearing nude mice. Conclusion: This study indicates that SUR-based nanocarrier might present a promising platform to reverse MDR in cancer chemotherapy. Keywords: multidrug resistance, cellular uptake, cellular efflux, biodistribution
format	article
author	Huang W Lang Y Hakeem Abdul Lei Y Gan L Yang X
author_facet	Huang W Lang Y Hakeem Abdul Lei Y Gan L Yang X
author_sort	Huang W
title	Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers
title_short	Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers
title_full	Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers
title_fullStr	Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers
title_full_unstemmed	Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers
title_sort	surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/ccf7c9786edd4f1db21346bfa096b5d0
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_version_	1718401821756620800

Surfactin-based nanoparticles loaded with doxorubicin to overcome multidrug resistance in cancers

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