Thymoquinone-loaded mesenchymal stem cell-derived exosome as an efficient nano-system against breast cancer cells

Objective(s): Exosomes became the subject of extensive research in drug delivery approach due to their potential applicability as therapeutic tools for cancer therapy. Thymoquinone (Tq) is an anti-cancer agent due to its great anti-proliferative effect. However, poor solubility and weak bioavailability restrict its therapeutic applications. In this study, exosomes secreted from human adipocyte-derived mesenchymal stem cells (AdMSCs) were isolated and the efficacy of a novel encapsulation method for loading of Tq was investigated. Finally, the cytotoxic effect of Tq incorporated exosomes against cancer cells was evaluated.Materials and Methods: Exosomes secreted from AdMSCs were isolated via ultracentrifugation and characterized by electron microscopy and western blotting. Then, through a novel encapsulation approach, Tq was loaded into exosomes by the combination of three methods including incubation, freeze-thawing, and surfactant treatment. Then, the encapsulation efficiency, in vitro cellular uptake, and cytotoxicity of Tq incorporated exosomes (Tq@EXOs) in MCF۷ and L۹۲۹ cells were estimated. Results: Tq loading into exosomes through our novel method caused a significant improvement in encapsulation efficiency of about ۶۰%. The fluorescent microscopy and flow cytometry outcomes indicated the efficient uptake of Tq@EXOs-FITC by cells throughout ۴ hr. Furthermore, MTT results displayed the ability of Tq@EXOs in effectively decreasing the cell viability of MCF۷ without causing any obvious cytotoxicity on L۹۲۹ as normal cells.Conclusion: The results suggest that our approach provides effective loading of Tq into exosomes which offer a valuable and safe platform for drug delivery to cancer cells thus having a great potential for clinical studies.  

Keywords:

Adipose-derived mesenchymal stem cells , Breast Cancer , Drug Delivery system , Exosome , Thymoquinone