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.