Modular plasmonic nanocarriers for efficient delivery of siRNA with spatial and temporal control (749.2)

Abstract

RNA interference (RNAi), a process that controls the flow of genetic information in cells, has been recognized for its potential in cancer therapeutic applications and stem cell differentiation related regenerative medicine. Yet the routine use of RNAi for disease treatment or prevention still calls for novel and efficient methods of delivery with spatial and temporal control. One of the most difficult hurdles to overcome for RNAi using nonviral vectors is endosomal escape into the cytosol, which is necessary for gene silencing to occur. We recently developed an approach using hollow gold nanoshells (HGNs) and near infrared (NIR) light: siRNAs were conjugated onto HGNs via quasi-covalent gold-thiol bond; laser illumination at a wavelength resonant with the nanoparticle plasmon (~800nm) triggered the release of siRNAs. Here we describe our further improvement of this approach through the use of targeting peptides to deliver the siRNA to specific cancer cells. We targeted the Polo-like kinase (PLK1), critical to centrosome maturation during mitosis, to induce a pro-apoptotic pathway in prostate cancer cells. We also developed a modular design to make the assembly of these siRNA delivery reagents more straightforward and inexpensive. We modified the targeting peptide approach by enclosing the HGN-siRNA with TAT-lipid and delivered the siRNA into human embryonic stem cells. Grant Funding Source: Supported by NIH grant R01 EB012637 and CIRM grant TG2-01151