Cationic Hyperbranched Polymers with Biocompatible Shells for siRNA Delivery.
Cationic Hyperbranched Polymers with Biocompatible Shells for siRNA Delivery.
复制标题
阳离子超支聚合物，具有生物相容性壳，用于siRNA递送。
DOI：
10.1021/acs.biomac.8b00902
复制
发表时间：
2018-09-10
影响因子：
6.2
通讯作者：
Matyjaszewski K
中科院分区：
文献类型：
--
作者：
Li S;Omi M;Cartieri F;Konkolewicz D;Mao G;Gao H;Averick SE;Mishina Y;Matyjaszewski K
以含季铵基团的原子转移自由基聚合(ATRP)亚胺为原料，通过自缩合乙烯基聚合法合成了阳离子超支化聚合物(HBP)。分别从HBP核接枝了两种生物相容性壳层：聚甲基丙烯酸寡乙二醇酯(PolyOEGMA)和聚甲基丙烯酸异丁二醇酯(PolyDMSO)，形成了低相对分子质量分散性和高生物相容性的核壳结构。两种结构均表现出较低的细胞毒性和良好的siRNA络合能力。评估了基因沉默对Run-Related转录因子2(Runx2)表达的有效性以及成骨细胞培养中矿化结节形成的长期评估。生物相容的核壳结构对于将有害的细胞毒性和非特异性基因抑制降至最低至关重要。由于壳层空间位阻较低，聚DMSO-HBP比PolyOEGMA-HBP具有更高的形成聚合物的效率。总体而言，这两种核壳结构的基因沉默效率与商业药物脂质体相当，表明基因沉默在治疗异位骨化(HO)方面具有长期潜力。
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).
登录
查看更多内容
影响因子：
6.2
作者：
Cho, Hong Y.;Averick, Saadyah E.;Matyjaszewski, Krzysztof
通讯作者：
Matyjaszewski, Krzysztof
影响因子：
5.5
作者：
Garnier, S;Laschewsky, A
通讯作者：
Laschewsky, A
影响因子：
18.3
作者：
Guo, Xia;Huang, Leaf
通讯作者：
Huang, Leaf
影响因子：
56.9
作者：
FRECHET, JMJ;HENMI, M;GRUBBS, RB
通讯作者：
GRUBBS, RB
影响因子：
6.2
作者：
Cho, Hong Y.;Gao, Haifeng;Matyjaszewski, Krzysztof
通讯作者：
Matyjaszewski, Krzysztof