Cancer Genomics

Biography

Biography: Hala Gali-Muhtasib

Abstract

Thymoquinone (TQ) is a promising anticancer molecule but its development is hindered by its limited bioavailability. Drug nanoparticle formulation is commonly used to overcome low drug solubility, limited bioavailability and nonspecific targeting. This project aimed at synthesizing different TQ nanoparticles (TQ-NP), characterizing them and assessing their uptake and delivery mechanisms as well as their anticancer potential in a panel of breast cancer cells. TQ-NP was prepared by flash nanoprecipitation. Dynamic light scattering and scanning electron microscopy were used for the characterization of the size, morphology and stability of the NPs. The anticancer activity was assessed by MTT. The uptake and subcellular intake mechanism of fluorescent TQ-NP were evaluated by both fluorometry and confocal microscopy. Four different TQ-NPs were formulated. The average diameter size ranged between 45-130 nm. All TQ-NPs were stable and had high entrapment efficiency (75-80%) and loading content (36-50%). In vitro, TQ-NP had equal or enhanced anticancer activity effects compared to TQ, in MCF-7 and aggressive MDA-MB-231 breast cancer cell lines. No significant cytotoxicity of the blank NP was noted. The uptake of fluorescent TQ-NP occurred in a time and concentration dependent manner. Treatment with inhibitors of endocytosis revealed the involvement of caveolin mediated endocytic pathway in TQ-NP uptake. This was also confirmed by subcellular localization findings, showing the colocalization of TQ-NP with both caveolin and transferrin as well as with the early and late markers of endocytosis, EEA-1 and lamp-1 proteins. Altogether, the results describe an approach for the enhancement of TQ anticancer activity and uncover the mechanisms behind cell-TQ-NP interaction, uptake and biodistribution.