TY - JOUR
T1 - Cationic Hyperbranched Polymers with Biocompatible Shells for siRNA Delivery
AU - Li, Sipei
AU - Omi, Maiko
AU - Cartieri, Francis
AU - Konkolewicz, Dominik
AU - Mao, Gordon
AU - Gao, Haifeng
AU - Averick, Saadyah E.
AU - Mishina, Yuji
AU - Matyjaszewski, Krzysztof
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/9/10
Y1 - 2018/9/10
N2 - 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).
AB - 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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U2 - 10.1021/acs.biomac.8b00902
DO - 10.1021/acs.biomac.8b00902
M3 - Article
C2 - 30148627
AN - SCOPUS:85052860432
SN - 1525-7797
VL - 19
SP - 3754
EP - 3765
JO - Biomacromolecules
JF - Biomacromolecules
IS - 9
ER -