Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells

Amoura M Abou-El-Naga,1 Ghada Mutawa,2 Ibrahim M El-Sherbiny,3 Shaker A Mousa4 1Zoology Department, Faculty of Sciences, Mansoura University, Mansoura 35516, Egypt; 2Department of Basic Science, Faculty of Dentistry, Horus University in Egypt (HUE), New Damietta 34517, Egypt; 3Center for Materials...

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Autores principales:	Abou-El-Naga AM, Mutawa G, El-Sherbiny IM, Mousa SA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	PLGA NPs Breast cancer Chemo-resistance Endocytosis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/148fa30fa8f646ef85c4040350d2e337
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spelling	oai:doaj.org-article:148fa30fa8f646ef85c4040350d2e3372021-12-02T08:10:14ZActivation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells1178-2013https://doaj.org/article/148fa30fa8f646ef85c4040350d2e3372018-11-01T00:00:00Zhttps://www.dovepress.com/activation-of-polymeric-nanoparticle-intracellular-targeting-overcomes-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Amoura M Abou-El-Naga,1 Ghada Mutawa,2 Ibrahim M El-Sherbiny,3 Shaker A Mousa4 1Zoology Department, Faculty of Sciences, Mansoura University, Mansoura 35516, Egypt; 2Department of Basic Science, Faculty of Dentistry, Horus University in Egypt (HUE), New Damietta 34517, Egypt; 3Center for Materials Science, Zewail City of Science and Technology, Cairo 12588, Egypt; 4The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA Background: Successfully overcoming obstacles due to anticancer drugs’ toxicity and achieving effective treatment using unique nanotechnology is challenging. The complex nature of breast tumors is mainly due to chemoresistance. Successful docetaxel (DTX) delivery by nanoparticles (NPs) through inhibition of multidrug resistance (MDR) can be a bridge to enhance intracellular dose and achieve higher cytotoxicity for cancer cells. Purpose: This study tested primary patient breast cancer cells in vitro with traditional free DTX in comparison with polymeric nanocarriers based on poly lactic co-glycolic acid (PLGA) NPs. Materials and methods: Establishment of primary cell line from breast malignant tumor depends on enzymatic digestion. Designed DTX-loaded PLGA NPs were prepared with a solvent evaporation method; one design was supported by the use of folic acid (FA) conjugated to PLGA. The physical properties of NPs were characterized as size, charge potential, surface morphology, DTX loading, and encapsulation efficiency. In vitro cellular uptake of fluorescent NPs was examined visually with confocal fluorescence microscopy and quantitatively with flow cytometry. In vitro cytotoxicity of all DTX designed NPs against cancer cells was investigated with MTT assay. RT-PCR measurements were done to examine the expression of chemoresistant and apoptotic genes of the tested DTX NPs. Results: Cellular uptake of DTX was time dependent and reached the maximum after loading on PLGA NPs and with FA incorporation, which activated the endocytosis mechanism. MTT assay revealed significant higher cytotoxicity of DTX-loaded FA/PLGA NPs with higher reduction of IC50 (8.29 nM). In addition, PLGA NPs, especially FA incorporated, limited DTX efflux by reducing expression of ABCG2 (3.2-fold) and MDR1 (2.86-fold), which were highly activated by free DTX. DTX-loaded FA/PLGA NPs showed the highest apoptotic effect through the activation of Caspase-9, Caspase-3, and TP53 genes by 2.8-, 1.6-, and 1.86-fold, respectively. Conclusion: FA/PLGA NPs could be a hopeful drug delivery system for DTX in breast cancer treatment. Keywords: PLGA NPs, chemoresistance, endocytosis, drug delivery system, active targeting, human breast cancer, DTX loaded PLGA NPsAbou-El-Naga AMMutawa GEl-Sherbiny IMMousa SADove Medical PressarticlePLGA NPsBreast cancerChemo-resistanceEndocytosisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 8153-8164 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	PLGA NPs Breast cancer Chemo-resistance Endocytosis Medicine (General) R5-920
spellingShingle	PLGA NPs Breast cancer Chemo-resistance Endocytosis Medicine (General) R5-920 Abou-El-Naga AM Mutawa G El-Sherbiny IM Mousa SA Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells
description	Amoura M Abou-El-Naga,1 Ghada Mutawa,2 Ibrahim M El-Sherbiny,3 Shaker A Mousa4 1Zoology Department, Faculty of Sciences, Mansoura University, Mansoura 35516, Egypt; 2Department of Basic Science, Faculty of Dentistry, Horus University in Egypt (HUE), New Damietta 34517, Egypt; 3Center for Materials Science, Zewail City of Science and Technology, Cairo 12588, Egypt; 4The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA Background: Successfully overcoming obstacles due to anticancer drugs’ toxicity and achieving effective treatment using unique nanotechnology is challenging. The complex nature of breast tumors is mainly due to chemoresistance. Successful docetaxel (DTX) delivery by nanoparticles (NPs) through inhibition of multidrug resistance (MDR) can be a bridge to enhance intracellular dose and achieve higher cytotoxicity for cancer cells. Purpose: This study tested primary patient breast cancer cells in vitro with traditional free DTX in comparison with polymeric nanocarriers based on poly lactic co-glycolic acid (PLGA) NPs. Materials and methods: Establishment of primary cell line from breast malignant tumor depends on enzymatic digestion. Designed DTX-loaded PLGA NPs were prepared with a solvent evaporation method; one design was supported by the use of folic acid (FA) conjugated to PLGA. The physical properties of NPs were characterized as size, charge potential, surface morphology, DTX loading, and encapsulation efficiency. In vitro cellular uptake of fluorescent NPs was examined visually with confocal fluorescence microscopy and quantitatively with flow cytometry. In vitro cytotoxicity of all DTX designed NPs against cancer cells was investigated with MTT assay. RT-PCR measurements were done to examine the expression of chemoresistant and apoptotic genes of the tested DTX NPs. Results: Cellular uptake of DTX was time dependent and reached the maximum after loading on PLGA NPs and with FA incorporation, which activated the endocytosis mechanism. MTT assay revealed significant higher cytotoxicity of DTX-loaded FA/PLGA NPs with higher reduction of IC50 (8.29 nM). In addition, PLGA NPs, especially FA incorporated, limited DTX efflux by reducing expression of ABCG2 (3.2-fold) and MDR1 (2.86-fold), which were highly activated by free DTX. DTX-loaded FA/PLGA NPs showed the highest apoptotic effect through the activation of Caspase-9, Caspase-3, and TP53 genes by 2.8-, 1.6-, and 1.86-fold, respectively. Conclusion: FA/PLGA NPs could be a hopeful drug delivery system for DTX in breast cancer treatment. Keywords: PLGA NPs, chemoresistance, endocytosis, drug delivery system, active targeting, human breast cancer, DTX loaded PLGA NPs
format	article
author	Abou-El-Naga AM Mutawa G El-Sherbiny IM Mousa SA
author_facet	Abou-El-Naga AM Mutawa G El-Sherbiny IM Mousa SA
author_sort	Abou-El-Naga AM
title	Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells
title_short	Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells
title_full	Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells
title_fullStr	Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells
title_full_unstemmed	Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells
title_sort	activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/148fa30fa8f646ef85c4040350d2e337
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_version_	1718398585966428160

Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells

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