Fabrication of folic acid-conjugated chitosan-coated PLGA nanoparticles for targeted delivery of Peganum harmala smoke extract to breast cancer cells

In this study, PLGA-NPs coated with folic acid-chitosan (PCF-NPs) loaded with Peganum harmala smoke extract (PSE) were synthesized (PSE-PCF-NPs), and their anti-cancer effects were evaluated. PSE-PCF-NPs were synthesized by the nanoprecipitation method and then characterized by DLS, SEM, and FTIR methods. HPLC and UV-vis spectroscopy were used to evaluate the PSE's folic acid (FA) binding and encapsulation. PSE-PCF-NPs-mediated cell viability and apoptosis were investigated by MTT, qPCR, flow cytometry, AO/PI, and DAPI staining. Anti-oxidant properties of PSE-PCF-NPs were evaluated by ABTS, DPPH, FRAP, and ROS. Angiogenic effects of PSE-PCF-NPs were assessed by CAM assay. The PSE-PCF-NPs (276.16 nm, PDI: 0.25, zeta-potential: +32.31 mV, FB: 67.6% and %EE: 89%) demonstrated selective toxicity on MCF-7 cells (IC50: 75.65 mu g ml(-1)). The occurrence of apoptosis in MCF-7 cells was confirmed by up-regulation of P53, Cas-3, and Cas-9 genes, increased SubG1 phase cells, and the results of fluorescent staining. Scavenging free radicals, reducing iron ions, increasing intracellular ROS, and decreasing SOD gene confirmed the anti- and pro-oxidant effects of PSE-PCF-NPs outside and inside MCF-7 cells. Reduction of angiogenic factors in CAM assay showed the anti-angiogenic effects of PSE-PCF-NPs. PSE-PCF-NPs, due to their anti-cancer properties, can be considered a therapeutic agent in cancer studies.