Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization

Mohammed M Mehanna,1,2,* Rana Sarieddine,3,* Jana K Alwattar,2 Racha Chouaib,3 Hala Gali-Muhtasib3 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon...

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Autores principales:	Mehanna MM, Sarieddine R, Alwattar JK, Chouaib R, Gali-Muhtasib H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	antitumor breast cancer cubosomes endocytosis nanoparticles thymoquinone uptake Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4e5958ca827a4cc78a0d40388833fe01
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spelling	oai:doaj.org-article:4e5958ca827a4cc78a0d40388833fe012021-12-02T12:01:47ZAnticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization1178-2013https://doaj.org/article/4e5958ca827a4cc78a0d40388833fe012020-12-01T00:00:00Zhttps://www.dovepress.com/anticancer-activity-of-thymoquinone-cubic-phase-nanoparticles-against--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mohammed M Mehanna,1,2,* Rana Sarieddine,3,* Jana K Alwattar,2 Racha Chouaib,3 Hala Gali-Muhtasib3 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 3Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon*These authors contributed equally to this workCorrespondence: Hala Gali-MuhtasibDepartment of Biology, Faculty of Arts and Sciences, American University of Beirut, Riad El Solh, Beirut 1107 2020, LebanonEmail amro@aub.edu.lbJana K AlwattarDepartment of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Riad El Solh, Beirut 1107 2020, LebanonEmail janawattar@gmail.comIntroduction: Triple negative breast cancer is an aggressive disorder which accounts for at least 15% of breast cancer diagnosis and a high percentage of breast cancer morbidity, hence intensive research efforts are focused on the development of effective therapies to overcome the disease. Thymoquinone (TQ), the bioactive constituent of Nigella sativa, exhibits anticancer activity, yet its translation to the clinic is hindered by its poor bioavailability and lack of quantification method in blood and tissues. To overcome these limitations, cubosomes were utilized for the encapsulation and delivery of this anticancer molecule.Methods: Thymoquinone loaded cubosomes were prepared through the emulsification homogenization method. The physicochemical characteristics, including particle size, zeta potential, morphology and entrapment efficiency, were studied. Moreover, the in vitro antitumor activity was tested on breast cancer cell lines (MCF-7 and MDA-MB-231) and compared to non-tumorigenic cell line (MCF-10A). Subcellular localization, cellular uptake and apoptotic effects of the formulations were assessed.Results: The results revealed that the TQ loaded cubosomal formulation exhibited a mean particle size of 98.0 ± 4.10 nm with narrow unimodal distribution. The high entrapment efficiency (96.60 ± 3.58%) and zeta potential (31.50 ± 4.20 mV) conceived the effectiveness of this nanosystem for TQ encapsulation. Cell viability in both breast cancer cell lines demonstrated a dose-dependent decrease in response to treatment with free TQ or TQ-loaded cubosomes, with enhanced antitumor activity upon treating with the latter formulation. A significant increase in apoptotic bodies and cleaved caspase 3 was observed upon treatment of MDA-MB-231 cells with either TQ or TQ-loaded cubosomes. Localization and trafficking studies unveiled that cubosomes accumulate in the cytoplasm of the studied breast cancer cell lines.Discussion: Our results show that thymoquinone encapsulation in cubosomal nanoparticles provides a promising anticancer drug delivery system with the ability to label, detect and subsequently trace it within the human cells.Keywords: antitumor, breast cancer, cubosomes, endocytosis, nanoparticles, thymoquinone, uptakeMehanna MMSarieddine RAlwattar JKChouaib RGali-Muhtasib HDove Medical Pressarticleantitumorbreast cancercubosomesendocytosisnanoparticlesthymoquinoneuptakeMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 9557-9570 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antitumor breast cancer cubosomes endocytosis nanoparticles thymoquinone uptake Medicine (General) R5-920
spellingShingle	antitumor breast cancer cubosomes endocytosis nanoparticles thymoquinone uptake Medicine (General) R5-920 Mehanna MM Sarieddine R Alwattar JK Chouaib R Gali-Muhtasib H Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization
description	Mohammed M Mehanna,1,2,* Rana Sarieddine,3,* Jana K Alwattar,2 Racha Chouaib,3 Hala Gali-Muhtasib3 1Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 3Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon*These authors contributed equally to this workCorrespondence: Hala Gali-MuhtasibDepartment of Biology, Faculty of Arts and Sciences, American University of Beirut, Riad El Solh, Beirut 1107 2020, LebanonEmail amro@aub.edu.lbJana K AlwattarDepartment of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Riad El Solh, Beirut 1107 2020, LebanonEmail janawattar@gmail.comIntroduction: Triple negative breast cancer is an aggressive disorder which accounts for at least 15% of breast cancer diagnosis and a high percentage of breast cancer morbidity, hence intensive research efforts are focused on the development of effective therapies to overcome the disease. Thymoquinone (TQ), the bioactive constituent of Nigella sativa, exhibits anticancer activity, yet its translation to the clinic is hindered by its poor bioavailability and lack of quantification method in blood and tissues. To overcome these limitations, cubosomes were utilized for the encapsulation and delivery of this anticancer molecule.Methods: Thymoquinone loaded cubosomes were prepared through the emulsification homogenization method. The physicochemical characteristics, including particle size, zeta potential, morphology and entrapment efficiency, were studied. Moreover, the in vitro antitumor activity was tested on breast cancer cell lines (MCF-7 and MDA-MB-231) and compared to non-tumorigenic cell line (MCF-10A). Subcellular localization, cellular uptake and apoptotic effects of the formulations were assessed.Results: The results revealed that the TQ loaded cubosomal formulation exhibited a mean particle size of 98.0 ± 4.10 nm with narrow unimodal distribution. The high entrapment efficiency (96.60 ± 3.58%) and zeta potential (31.50 ± 4.20 mV) conceived the effectiveness of this nanosystem for TQ encapsulation. Cell viability in both breast cancer cell lines demonstrated a dose-dependent decrease in response to treatment with free TQ or TQ-loaded cubosomes, with enhanced antitumor activity upon treating with the latter formulation. A significant increase in apoptotic bodies and cleaved caspase 3 was observed upon treatment of MDA-MB-231 cells with either TQ or TQ-loaded cubosomes. Localization and trafficking studies unveiled that cubosomes accumulate in the cytoplasm of the studied breast cancer cell lines.Discussion: Our results show that thymoquinone encapsulation in cubosomal nanoparticles provides a promising anticancer drug delivery system with the ability to label, detect and subsequently trace it within the human cells.Keywords: antitumor, breast cancer, cubosomes, endocytosis, nanoparticles, thymoquinone, uptake
format	article
author	Mehanna MM Sarieddine R Alwattar JK Chouaib R Gali-Muhtasib H
author_facet	Mehanna MM Sarieddine R Alwattar JK Chouaib R Gali-Muhtasib H
author_sort	Mehanna MM
title	Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization
title_short	Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization
title_full	Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization
title_fullStr	Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization
title_full_unstemmed	Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization
title_sort	anticancer activity of thymoquinone cubic phase nanoparticles against human breast cancer: formulation, cytotoxicity and subcellular localization
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/4e5958ca827a4cc78a0d40388833fe01
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Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization

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