Monodispersed Brush-Like Conjugated Polyelectrolyte Nanoparticles with Efficient and Visualized SiRNA Delivery for Gene Silencing

Citations Over TimeTop 10% of 2013 papers

Abstract

RNA interference is supposed to be one of the most powerful technologies for suppression of genes and treatment of diverse human diseases while the safe delivery and visualization of siRNA were still challenging. In this text, a novel type of monodispersed conjugated polymer nanoparticles PFNBr with brush-like molecular structure was introduced into siRNA delivery system. The nanoparticles exhibited dual functions conveniently in the delivery system which can not only carry high amount of siRNA to penetrate intracellularly for knocking down targeted mRNA but also act as signal agents for siRNA tracking and cellular imaging. Due to the high density side chains with positive charges and more extended conformation of the spatial structure, PFNBr nanoparticles as nanocarrier for siRNA provided outstanding capture ability (1 mol polymer to more than 32.5 mol siRNA) and enhanced protection capability of siRNA molecules from degradation. Here, it should be noted that the concentration of carrier in the working platform was lowered from the level of μmol/L to nmol/L compared with other conjugated polymer delivery systems due to the outstanding carrying capacity of PFNBr. And meanwhile, this system acquired high gene silence efficiency and good biocompatibility. The proposed complex nanoparticles efficiently transfected siPlk1 into PANC-1 cells and induced high knockdown efficiency for targeted Plk1 mRNA to 23.9% and no significant cytotoxicity of the PFNBr/siRNA complexes was shown. Therefore, this working platform provides a solution to most of the common problems associated with the siRNA delivery, visualization, and therapeutic applications, and keeps a bright outlook for the development of new nucleic acid-based therapeutics and simultaneously for fluorescent bioimaging.

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