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Cationic Hyperbranched Polymers with Biocompatible Shells for siRNA Delivery
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-08-27 00:00:00 , DOI: 10.1021/acs.biomac.8b00902
Sipei Li 1 , Maiko Omi 2 , Francis Cartieri 3 , Dominik Konkolewicz 4 , Gordon Mao 3 , Haifeng Gao 5 , Saadyah E. Averick 3 , Yuji Mishina 2 , Krzysztof Matyjaszewski 1
Affiliation  

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).

中文翻译:

具有生物相容性外壳的阳离子超支化聚合物,可用于siRNA递送。

阳离子超支化聚合物(HBP)是通过含缩季胺基团的原子转移自由基聚合(ATRP)单体的乙烯基缩聚反应制得的。从HBP核分别接枝了两种类型的生物相容壳,分别是聚甲基丙烯酸低聚乙二醇(polyOEGMA)和聚甲基丙烯酸2-(甲基亚砜基)乙酯(polyDMSO),以形成分子量分散性低且生物相容性高的核-壳结构。 ,polyOEGMA–HBP和polyDMSO–HBP。两种结构均显示出低细胞毒性和良好的siRNA络合能力。基因沉默对抗Runt相关转录因子2(Runx2)的功效表达和长期评估成骨细胞培养中的矿化结节形成。生物相容性核壳结构对于最大程度地减少不良细胞毒性和非特异性基因抑制至关重要。由于壳的位阻较低,polyDMSO–HBP形成多链体的功效比polyOEGMA–HBP高。总体而言,两个核-壳结构的基因沉默效率均与商业试剂Lipofectamine相当,表明基因沉默可用于治疗异位骨化(HO)的长期潜力。
更新日期:2018-08-27
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