Synthesis and biological activity of siRNA and Etoposide with magnetic nanoparticles on drug resistance model MCF-۷ Cells: Molecular docking study with MRP۱ enzyme

Objective(s): In this work, MRP-۱ (Multidrug resistance-associated protein ۱) gene expression levels and anticancer activity of siRNA and Etoposide loaded Poly-hydroxybutyrate (PHB) coated magnetic nanoparticles (MNPs) was studied on MCF-۷/Sensitive and MCF-۷/۱۰۰۰Etoposide resistance cells. For this purpose, PHB covered iron oxide-based magnetic nanoparticles (PHB-MNPs) were prepared by coprecipitation. We used magnetic nanoparticles because they include highly targeted to tumors in vivo cancer therapy. Materials and Methods: Etoposide, anti-cancer drug, was loaded onto the PHB-MNPs. The in vitro cytotoxicity analysis of siRNA and Etoposide-loaded PHB-MNPs was applied on cancer cells. The expression levels of MRP۱ related to drug resistance were shown using qRT-PCR. In the present study, we also investigated whether nanoparticle system could be a potential anticancer drug target with molecular docking analyses.Results: The IC۵۰ values of Etoposide on MCF-۷/sensitive and MCF-۷/۱۰۰۰Eto resistance cells were identified as ۵۰,۶ μM and ۱۳۵,۷ μM, respectively. IC۵۰ values of siRNA and Etoposide loaded PHB coated magnetic nanoparticles were determined as ۱۰,۱۸ μM and ۳۹,۲۱ μM on MCF-۷ and MCF-۷/۱۰۰۰ Eto cells, respectively. According to the gene expression results, MRP۱ expression was ۴ fold upregulated in MCF-۷/۱۰۰۰Eto cells. However, it was about ۳ fold downregulated due to the application of siRNA-Etoposide loaded magnetic nanoparticles. Conclusion: According to the docking results, nanoparticle system may be a drug active substance with obtained results. The results of this study demonstrated that siRNA and Etoposide loaded PHB covered iron oxide based magnetic nanoparticles can be a potential targeted therapeutic agent to overcome drug resistance.

Keywords:

Anticancer effect , Breast Cancer , Etoposide , Molecular docking , PHB coated magnetic nanoparticles , siRNA