Abstract 2053: Effects of thymoquinone encapsulation on its uptake, delivery and anticancer activity in breast cancer cells

Introduction: Thymoquinone (TQ) is a promising anticancer molecule which suffers from limited bioavailability. Drug encapsulation is commonly used to overcome low drug solubility, bioavailability as well as nonspecific targeting. For this project, we synthesized different TQ nanoparticles (TQ-NPs), characterized their properties, uptake and delivery mechanisms, and assessed their anticancer potential in a panel of breast cancer cells.

Methods: The different TQ-NPs were prepared using Flash nanoprecipitation. Dynamic light scattering and scanning electron microscope were used for the characterization of the size, morphology and stability of the NPs. The anticancer effect was assessed by MTT. We subsequently formulated fluorescent TQ-NPs and evaluated their uptake and subcellular intake mechanism by both fluorometry and confocal microscopy.

Results: We were successful at formulating four different stable TQ-NPs that had an average diameter size between 45-130 nm. All TQ-NPs had also high entrapment efficiency and loading content. In vitro, TQ-NPs enhanced the antitumor activity of the drug in both MCF-7 and MDA-MB-231 cells, when compared to free TQ with no significant cytotoxicity of the blank NPs. Fluorescent TQ-NPs uptake was further found to be both time and concentration dependent. Finally, using inhibitors of endocytosis we determined that the endocytosis of TQ-NPs is caveolin mediated. This was also confirmed by examining the subcellular localization of TQ-NPs. The nanoparticle formulations colocalized with both caveolin and transferrin but not with lamp-1 and EEA-1 proteins.

Conclusion: Altogether, our results describe a new approach for the enhancement of TQ anticancer activity and provide insights on the uptake dynamics specific to our formulation.

Citation Format: Isabelle Fakhoury, Walid Saad, Kamal Bou Hadir, Regine Schneider-Stock, Hala Gali-Muhtasib. Effects of thymoquinone encapsulation on its uptake, delivery and anticancer activity in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2053.