Effective gene silencing by multilayered siRNA-coated gold nanoparticles

Small interfering RNA (siRNA) has been widely proposed to treat various diseases by silencing genes, but its delivery remains a challenge. A well controlled assembly approach is applied to prepare a protease-assisted nanodelivery system. Protease-degradable poly-L-lysine (PLL) and siRNA are fabricated onto gold nanoparticles (AuNPs), by alternating the charged polyelectrolytes. In this study, up to 4 layers of PLL and 3 layers of siRNA (sR3P) are coated. Due to the slow degradation of PLL, the incorporated siRNA is released gradually and shows extended gene-silencing effects. Importantly, the inhibition effect in cells is found to correlate with the number of siRNA layers. A layering approach to deliver small interfering RNA (siRNA) with an extended gene-silencing effect is developed. Multilayers of siRNA are fabricated on a nanometer-sized core with a protease-sensitive polypeptide, which can be degraded gradually by intracellular protease, resulting in a prolonged siRNA effect.