Cationic Hyperbranched Polymers with Biocompatible Shells for siRNA Delivery
2018
Li, Sipei | Omi, Maiko | Cartieri, Francis | Konkolewicz, Dominik | Mao, Gordon | Gao, Haifeng | Averick, Saadyah E. | Mishina, Yuji | Matyjaszewski, K. (Krzysztof)
Cationic hyperbranched polymers (HBP) were prepared by self-condensing vinyl polymerization of an atom transfer radical polymerization (ATRP) inimer containing a quaternary ammonium group. Two types of biocompatible shells, poly(oligoethylene glycol) methacrylate (polyOEGMA) and poly(2-(methylsulfinyl) ethyl methacrylate) (polyDMSO), were grafted respectively from HBP core to form core–shell structures with low molecular weight dispersity and high biocompatibility, polyOEGMA–HBP and polyDMSO–HBP. Both of the structures showed low cytotoxicity and good siRNA complexing ability. The efficacy of gene silencing against Runt-related transcription factor 2 (Runx2) expression and the long-term assessment of mineralized nodule formation in osteoblast cultures were evaluated. The biocompatible core–shell structures were crucial to minimizing undesired cytotoxicity and nonspecific gene suppression. polyDMSO–HBP showed higher efficacy of forming polyplexes than polyOEGMA–HBP due to shell with lower steric hindrance. Overall, the gene silencing efficiency of both core–shell structures was comparable to commercial agent Lipofectamine, indicating long-term potential for gene silencing to treat heterotopic ossification (HO).
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