Increased Pro-Apoptotic and Anti-Proliferative Activities of Simvastatin Encapsulated PCL-PEG Nanoparticles on Human Breast Cancer Adenocarcinoma Cells

Recently, Simvastatin (SIM) is received notable attention due to its anti-cancer properties. However, the lipophilicity feature of SIM restricted its application as a chemotherapy agent. This work aimed to investigate the Polycaprolactone-Polyethylene Glycol (PCL-PEG) efficiency as the nano-carrier for SIM to enhance its anti-cancer properties. Dynamic Light Scattering (DLS), field emission scanning electron microscopy (FE-SEM), and Fourier transform infrared (FTIR) were used to characterize drug-loaded nanoparticles (NPs). To study apoptotic and anti-proliferative properties of drug-loaded NPs, flow cytometry and MTT assays were utilized. The real-time PCR method measured the expression of apoptotic genes Bcl-2, Bax, Fas and cell cycle regulating genes, p53, cyclin D, and Rb. MTT assay indicated that loading SIM on PCL-PEG NPs increased cytotoxicity dose-dependently. In addition, a noticeable increase was found in the sub- G1 population of treated cells with drug-loaded NPs than free SIM. The remarkable up-regulation of Bax, Fas and p53 genes was detected in treated MCF-7 cells with the decrease of Bcl2, Rb, and Cyclin D 1 gene expression in cells treated with drug-loaded NPs than free SIM. Taken together, these results show that the polymeric PCL-PEG NPs systems represent a promising new therapeutic approach for the treatment of breast cancer.