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.
KeywordsGold nanoparticles Targeting ligands Receptor-mediated internalization Non-viral siRNA delivery Prostate cancer Gene therapy
We acknowledge the financial support from Science Foundation Ireland and AMBER (Grant 12/RC/2278); the Irish Research Council, for a Government of Ireland Postdoctoral Fellowship (GOIPD/2013/150) and the Outstanding Youth Foundation from the Department of Science and Technology, Jilin Province (Project Number: 20170520046JH), to Jianfeng Guo; and the National Council for Scientific Research Lebanon (CNRS-L-GRP2015).
- 2.WKNg V, Berti R, Lesage F, Kakkar A (2013) Gold: a versatile tool for in vivo imaging. J Mater Chem B 1:9–25Google Scholar