Department of Chemistry , Carnegie Mellon University , 4400 Fifth Avenue , Pittsburgh , Pennsylvania 15213 , United States.
Department of Biological and Materials Sciences , University of Michigan , 1011 N. University , Ann Arbor , Michigan 48109 , United States.
Biomacromolecules. 2018 Sep 10;19(9):3754-3765. doi: 10.1021/acs.biomac.8b00902. Epub 2018 Aug 27.
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).
阳离子超支化聚合物（HBP）是通过含有季铵基团的原子转移自由基聚合（ATRP）引发剂的自缩乙烯聚合制备的。两种类型的生物相容性壳，聚（甲基丙烯酸聚乙二醇酯）（polyOEGMA）和聚（2-（甲基亚磺酰基）乙基甲基丙烯酸酯）（polyDMSO），分别从 HBP 核上接枝，形成具有低分子量分散度和高生物相容性的核壳结构，即 polyOEGMA-HBP 和 polyDMSO-HBP。这两种结构均表现出低细胞毒性和良好的 siRNA 复合能力。评估了针对 Runt 相关转录因子 2（Runx2）表达的基因沉默效果以及成骨细胞培养中矿化结节形成的长期评估。生物相容性的核壳结构对于最小化不需要的细胞毒性和非特异性基因抑制至关重要。由于壳层的空间位阻较小，polyDMSO-HBP 形成的聚合物比 polyOEGMA-HBP 具有更高的形成多聚物的效率。总的来说，这两种核壳结构的基因沉默效率与商业试剂 Lipofectamine 相当，表明其在治疗异位骨化（HO）方面具有长期的基因沉默潜力。
