Delivery of EGFR-siRNA to prostatic cancerous cells based on polydopamine coated gold nanoparticles

Common treatment of metastatic prostate cancer is limited to androgen deprivation (AD) therapy and chemotherapeutic agents, while the 5-year survival rate is less than 30%. The role of EGFR in metastasis and drug resistance of prostate cancer has been well reported. In this regard, small interfering RNA (siRNA) could be an efficacious strategy for improving the therapeutic outcomes against metastatic prostate cancer. However, the clinical application of siRNA over the decades has not been achieved due to various challenges such as stability, targeting, and transfection into the cancer cells. To overcome these, herein a nanocarrier delivery system for EGFR-siRNA based on gold nanoparticles coated with polydopamine (GNP-PDA) has been developed. The nanocarrier was prepared by polymerization of dopamine, a mussel adhesive protein, on the surface of GNPs. The GNP-PDA was able to properly complex with EGFR-siRNA. The GNP-PDA/EGFR-siRNA, with 55.59 ± 11.53 nm particle size and a negative surface charge, could retard the siRNA for 2 h studied through gel retardation assay. The flowcytometry and confocal microscopy demonstrated a high cellular uptake (>93%) over 2 h incubation with PC3 cells. The MTT assay further revealed that the PDA coating decreases the cytotoxicity of GNPs significantly. The GNP-PDA/EGFR-siRNA nanocomplex, at low concentration, showed 60% cytotoxicity, 55% apoptosis and 50.9% gene knockdown after 24 h incubation of the samples in PC3 cells. In conclusion, polydopamine-coated gold nanoparticles could be applied as a safe and efficient nano carrier for siRNA delivery to solid tumors.