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

Abstract

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.

Thymoquinone upregulates miR‐125a‐5p, attenuates STAT3 activation, and potentiates doxorubicin antitumor activity in murine solid Ehrlich carcinoma

“…Furthermore, encapsulating TQ in cubosomal nanoparticles can enhance its antitumor activity by improving the efficient delivery of this compound to target tissues. [136] Consistent with our findings, TQ was also found to exhibit antiproliferative and apoptotic activities in different types of cancer cells via blocking STAT3 activation. This attenuated the transcription and translation of STAT3-regulated targets such as survivin and cyclin D1, inducing G1 phase arrest and caspase-3,7,9 activation.…”

Preparation, characterization, and biological activity study of thymoquinone-cucurbit[7]uril inclusion complex

“…TQ, either free, encapsulated in a nanocarrier or in combination with other chemotherapeutics, is very promising against many cancers including cancer stem cells. [39][40][41] Moreover, the results also conrmed the low toxicity of CB [7] that supports the use of CB [7] as a drug carrier. Previously described reports about toxicity and safety of CB[n] demonstrated the relative safety and acceptable toxicity in vitro and in vivo.42,43 For example, Oun et al reported the lack of signicant tissue specic toxicity of CB [6] and CB [7] using ex Fig.…”

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

“…The synergistic potential of TQ loaded in cockle-shell-derived aragonite CaCl 3 -NPs was reported with doxorubicin to reduce cellular migration in mammary gland carcinoma stem cells (MDA MB 231) [ 186 ]. A cubosomal formulation of TQ improved cellular accumulation, which leads to increased apoptotic activity migration in mammary gland carcinoma cell lines (MDA-MB-231 and MCF-7) [ 187 ]. Chitosan-coated TQ-PLGA-NPs accumulated in melanoma cancer cells (A375) by taking advantage of the EPR effect and positive surface charge of chitosan, which facilitate binding with the negatively charged cell membrane and induce cellular retention as well as time-dependent cytotoxicity [ 188 ].…”