Bioconjugated Gold Nanoparticles Enhance siRNA Delivery in Prostate Cancer Cells

Here we describe a simple way to create a gold nanoparticle (AuNP)-based non-viral delivery system to deliver siRNA into prostate cancer cells. Therefore, positively charged polyethylenimine (PEI)-capped AuNPs were synthesized in water and further conjugated with the targeting ligand (folic acid) for folate receptors (AuNPs-PEI-FA). The AuNPs-PEI-FA could effectively complex small interfering RNA (siRNA) through electrostatic interaction. Flow cytometry displayed that AuNPs-PEI-FA could specifically deliver siRNA into LNCaP cells, a prostate cancer cell line overexpressing prostate-specific membrane antigen (PSMA) that exhibits a hydrolase enzymatic activity with a folate substrate. In contrast, internalization of siRNA into PC-3 cells, a prostate cancer cell line not expressing PSMA or folate receptors, was not achieved using AuNPs-PEI-FA.siRNA. Following endolysosomal escape, the AuNPs-PEI-FA-.siRNA formulation resulted in significant endogenous gene silencing when compared to the nontargeted formulation, suggesting the potential of AuNPs-PEI-FA for targeted delivery of therapeutic siRNAs in the treatment of prostate cancer.