Designing Salvigenin -loaded mPEG-b-PLGA @Fe3O4 nanoparticles system for improvement of Salvigenin anti-cancer effects on the breast cancer cells, an in vitro study

Slavigenin, a natural flavonoid, is a potent anti-cancer agent against various human cancer cell lines. However, its hydrophobic nature, low bioavailability limit its utilization for the medical treatment of cancer cells. In the present study, to overcome the limitations and increase its therapeutic efficacy, Salvigenin loaded mPEG-b-PLGA coated iron oxide nanoparticles (Sal loaded PLGA@Fe3O4 NPs) were designed. Physicochemical properties were investigated by Thermogravimetric analysis (TGA), Dynamic light scattering (DLS) and Transmission Electron Microscope (TEM). The Nanoparticles drug loading, entrapment efficiency, and drug release profile were measured in vitro. Their anticancer activity was determined on MDA-MB-231 and MCF7 human breast cancer cells and the results were confirmed by apoptotic detection tests. The results indicated that Salvigenin has been entrapped in mPEG-b-PLGA @Fe3O4 NPs with the efficacy of 82 +/- 1.6% while the NPs size was around 57 +/- 2 nm. In vitro release investigation showed sustained release pattern in buffer phosphate. The MTT assay indicated that the NPs exhibited a significant decrease in the MCF7 and MDA-MB-231 cells viability with IC50 concentrations of 74.2 +/-.8 mu M and 99.4 +/- 1.7 mu M respectively. This effect was mediated by apoptosis as confirmed by Annexin V/PI analysis and cell cycle arrest at the Sub-G1 stage. Western blot analyses showed significant downregulation of Bcl2 and up-regulation of Bax and Caspase-3 expression in the NPs treated cells. In conclusion, Sal loaded mPEG-b-PLGA @ Fe3O4 nanoparticles exhibited superior anticancer activity in breast cancer chemotherapy and could thus be a potential option for various kinds of cancer treatment.