Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization
Authors Mehanna MM, Sarieddine R, Alwattar JK, Chouaib R, Gali-Muhtasib H
Received 25 June 2020
Accepted for publication 15 September 2020
Published 1 December 2020 Volume 2020:15 Pages 9557—9570
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Thomas J. Webster
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 work
Correspondence: Hala Gali-Muhtasib
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Riad El Solh, Beirut 1107 2020, Lebanon
Jana K Alwattar
Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Riad El Solh, Beirut 1107 2020, Lebanon
Introduction: 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
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