Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies

Bo Li1, Hui Xu2, Zhen Li1, Mingfei Yao1, Meng Xie1, Haijun Shen1, Song Shen1, Xinshi Wang1, Yi Jin11College of Pharmaceutical sciences, Zhejiang University, Hangzhou, 2No. 202 Hospital of People&#39;s Liberation Army, Shenyang, ChinaBackground: Multidrug resistance (MDR) mediated by the over...

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Autores principales:	Li B, Xu H, Li Z, Yao M, Xie M, Shen H, Shen S, Wang X, Jin Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cf72ae370cf448c0a1ddda777e398844
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spelling	oai:doaj.org-article:cf72ae370cf448c0a1ddda777e3988442021-12-02T04:59:15ZBypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies1176-91141178-2013https://doaj.org/article/cf72ae370cf448c0a1ddda777e3988442012-01-01T00:00:00Zhttp://www.dovepress.com/bypassing-multidrug-resistance-in-human-breast-cancer-cells-with-lipid-a9022https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Bo Li1, Hui Xu2, Zhen Li1, Mingfei Yao1, Meng Xie1, Haijun Shen1, Song Shen1, Xinshi Wang1, Yi Jin11College of Pharmaceutical sciences, Zhejiang University, Hangzhou, 2No. 202 Hospital of People&#39;s Liberation Army, Shenyang, ChinaBackground: Multidrug resistance (MDR) mediated by the overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), remains one of the major obstacles to effective cancer chemotherapy. In this study, lipid/particle assemblies named LipoParticles (LNPs), consisting of a dimethyldidodecylammonium bromide (DMAB)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticle core surrounded by a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) shell, were specially designed for anticancer drugs to bypass MDR in human breast cancer cells that overexpress P-gp.Methods: Doxorubicin (DOX), a chemotherapy drug that is a P-gp substrate, was conjugated to PLGA and encapsulated in the self-assembled LNP structure. Physiochemical properties of the DOX-loaded LNPs were characterized in vitro. Cellular uptake, intracellular accumulation, and cytotoxicity were compared in parental Michigan Cancer Foundation (MCF)-7 cells and P-gp-overexpressing, resistant MCF-7/adriamycin (MCF-7/ADR) cells.Results: This study found that the DOX formulated in LNPs showed a significantly increased accumulation in the nuclei of drug-resistant cells relative to the free drug, indicating that LNPs could alter intracellular traffic and bypass drug efflux. The cytotoxicity of DOX loaded-LNPs had a 30-fold lower half maximal inhibitory concentration (IC50) value than free DOX in MCF-7/ADR, measured by the colorimetric cell viability (MTT) assay, correlated with the strong nuclear retention of the drug.Conclusion: The results show that this core-shell lipid/particle structure could be a promising strategy to bypass MDR.Keywords: chemotherapy, drug delivery, polymeric nanoparticles, multidrug resistanceLi BXu HLi ZYao MXie MShen HShen SWang XJin YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 187-197 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li B Xu H Li Z Yao M Xie M Shen H Shen S Wang X Jin Y Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies
description	Bo Li1, Hui Xu2, Zhen Li1, Mingfei Yao1, Meng Xie1, Haijun Shen1, Song Shen1, Xinshi Wang1, Yi Jin11College of Pharmaceutical sciences, Zhejiang University, Hangzhou, 2No. 202 Hospital of People&#39;s Liberation Army, Shenyang, ChinaBackground: Multidrug resistance (MDR) mediated by the overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), remains one of the major obstacles to effective cancer chemotherapy. In this study, lipid/particle assemblies named LipoParticles (LNPs), consisting of a dimethyldidodecylammonium bromide (DMAB)-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticle core surrounded by a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) shell, were specially designed for anticancer drugs to bypass MDR in human breast cancer cells that overexpress P-gp.Methods: Doxorubicin (DOX), a chemotherapy drug that is a P-gp substrate, was conjugated to PLGA and encapsulated in the self-assembled LNP structure. Physiochemical properties of the DOX-loaded LNPs were characterized in vitro. Cellular uptake, intracellular accumulation, and cytotoxicity were compared in parental Michigan Cancer Foundation (MCF)-7 cells and P-gp-overexpressing, resistant MCF-7/adriamycin (MCF-7/ADR) cells.Results: This study found that the DOX formulated in LNPs showed a significantly increased accumulation in the nuclei of drug-resistant cells relative to the free drug, indicating that LNPs could alter intracellular traffic and bypass drug efflux. The cytotoxicity of DOX loaded-LNPs had a 30-fold lower half maximal inhibitory concentration (IC50) value than free DOX in MCF-7/ADR, measured by the colorimetric cell viability (MTT) assay, correlated with the strong nuclear retention of the drug.Conclusion: The results show that this core-shell lipid/particle structure could be a promising strategy to bypass MDR.Keywords: chemotherapy, drug delivery, polymeric nanoparticles, multidrug resistance
format	article
author	Li B Xu H Li Z Yao M Xie M Shen H Shen S Wang X Jin Y
author_facet	Li B Xu H Li Z Yao M Xie M Shen H Shen S Wang X Jin Y
author_sort	Li B
title	Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies
title_short	Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies
title_full	Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies
title_fullStr	Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies
title_full_unstemmed	Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies
title_sort	bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/cf72ae370cf448c0a1ddda777e398844
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Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies

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