Polyelectrolyte-Gold Nanorod Assemblies for Transgene Delivery

Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal therapy and transgene delivery for cancer diseases. We have generated polyelectrolyte-functionalized gold nanorods (PE-GNRs) using a layer-by-layer deposition approach; a cationic polyelectrolyte library recently synthesized in our laboratory was employed to generate the PE-GNR assemblies. PE-GNR assemblies demonstrate long-term colloidal stability as well as the capacity to bind plasmid DNA by means of electrostatic interactions. Sub-toxic concentrations of PE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PE-GNRs generated using cationic polymers from our laboratory demonstrated higher transgene expression and exhibited lower cytotoxicities when compared to PE-GNRs generated using polyethylenimine (pEI), a current standard for polymer-mediated gene delivery. The role of polyelectrolyte chemistry, particle size, and zeta-potential on transgene expression efficacies of PE-GNRs was investigated. Plasmonic properties of gold nanorods were exploited for dark-field imaging of the delivered PE-GNRs. In addition, the stable photothermal properties of gold nanorods were exploited to investigate the role of GNR-induced hyperthermia in enhancing polymer-mediated transgene expression. Our results indicate that PE-GNRs are a promising engineered platform that demonstrate high stabilities, low cytotoxicities and enhanced transgene expression efficacies.  PE-GNRs also have the potential to be used simultaneously for photothermal ablation, photothermally enhanced drug and gene delivery, and biological imaging, thus making them a powerful theranostic platform.