Photo-Cleavable Polycations-Wrapped Upconversion Nanoparticles for Efficient siRNA Delivery and Cancer Therapy

RNA interference (RNAi) therapy is a promising approach for cancer therapy. However, due to the weak binding affinity between a carrier and small interference RNA (siRNA) and complicated tumor environment, efficient loading and release of siRNA still remain challenging. Here, we design photo-cleavable polycations-wrapped upconversion nanoparticles (PC-UCNPs) for spatially and temporally controllable siRNA delivery. The PC-UCNPs are synthesized by in situ reversible addition−fragmentation chain transfer (RAFT) polymerization of photo-cleaved 5-(2-(dimethylamino)ethoxy)-2-nitrobenzyl acrylat (MENA) monomer and poly(oligo(ethylene oxide) methyl ether acrylate (OEMA) mononer through a chain transfer agent that anchored on the surface of silica-coated upconversion nanoparticles (UCNPs@SiO2). After reacting with CH3I, siRNA and hyaluronic acid (HA) are adsorbed on the particle surface to prepare PC-UCNPs/siRNA/HA. The reaction with cell-secreted hyaluronidase (HAase) achieves the intracellular delivery of PC-UCNPs/siRNA/HA, and 980 nm laser irradiation causes siRNA release, which effectively improves the gene silencing efficiency in vitro and suppresses tumor growth in vivo; therefore, these processes have a promising potential application in precision medicine.