The Selective Anti-Breast Cancer Properties of the Folate-Chitosan-coated PLGA-stylosin Nanoparticles (Fcps-Nps)

Background The selective phytochemical-mediated anticancer treatment strategies based on nano-drug delivery systems have opened promising horizons for efficiently targeting cancer cells and improving the bioactive properties of their non-polar cargoes. In the current study, stylosine, the famous anticancer, terpene was loaded into the folate-chitosan-coated PLGA nanoparticles to evaluate their antioxidant, anti-angiogenic, and cytotoxic impact on human cancer cell lines (Hella, PANC, A2780, HT-29, and MCF-7). Materials and Methods The folate-chitosan-coated PLGA-stylosin nanoparticles (fCPS-NPs) were designed and produced in a multistep process applying the ultrasound homogenizing method. The FCPS-NPs were characterized by applying DLS, FESEM, FTIR, and Zeta-potential techniques. The nanoparticles’ antioxidant activity was studied by conducting ABTS-DPPH antioxidant assays and measuring the SOD gene expression profile in MCF-7 cancer cells. The impact of FCPS-NPs on cancer cell survival and CAM blood vessel angiogenesis was measured by applying MTT and CAM assays. Flow cytometry analysis was conducted to determine the cell death type. Finally, to verify the apoptotic death and anti-angiogenic molecular mechanism of FCPS-NPs, the BCL-2 and VEGF/VEGFR gene expression profiles were analyzed in MCF-7 cancer cells and CAM tissue, respectively. Results The 202.66-nm mono-dispersed FCPS-NPs with + 34.35 mV surface charge selectively induced significant apoptotic death in human breast MCF-7 cancer cells compared with other cancerous PANC and normal Huvec cell lines by increasing the SubG1 phase- arrested MCF-7 cells and down-regulating their anti-apoptotic BCL-2 gene expression. The FCPS-NPs exhibited meaningful antioxidant activity by inducing SOD-upregulation in the MCF-7 cells and strongly scavenging both ABTS and DPPH free radicals. Finally, the nanoparticles reduced the CAM blood vessels’ length and number, indicating their anti-angiogenic activity. Finally, the FCPS-NPs’ anti-angiogenic activity was verified by detecting the VEGF and VEGFR down-regulation in treated MCF-7 cancer cells. Conclusion The FCPS-NPs induced significant selective apoptotic death in human breast MCF-7 cancer cells, protected the cells by scavenging external free radicals, and improved the internal cell antioxidant defense system (SOD upregulation). The FCPS-NPs have the potential to be used as an efficient selective anti-breast cancer compound due to their antioxidant, selective cytotoxicity, and anti-angiogenic activities.