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合成具有阳离子和可降解核的生物相容性 PEG 基星形聚合物用于 siRNA 递送。

Synthesis of biocompatible PEG-Based star polymers with cationic and degradable core for siRNA delivery.

机构信息

Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States.

出版信息

Biomacromolecules. 2011 Oct 10;12(10):3478-86. doi: 10.1021/bm2006455. Epub 2011 Sep 6.

DOI:10.1021/bm2006455
PMID:21894897
Abstract

Star polymers with poly(ethylene glycol) (PEG) arms and a degradable cationic core were synthesized by the atom transfer radical copolymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate macromonomer (PEGMA), 2-(dimethylamino)ethyl methacrylate (DMAEMA), and a disulfide dimethacrylate (cross-linker, SS) via an "arm-first" approach. The star polymers had a diameter ~15 nm and were degraded under redox conditions by glutathione treatment into individual polymeric chains due to cleavage of the disulfide cross-linker, as confirmed by dynamic light scattering. The star polymers were cultured with mouse calvarial preosteoblast-like cells, embryonic day 1, subclone 4 (MC3T3-E1.4) to determine biocompatibility. Data suggest star polymers were biocompatible, with ≥ 80% cell viability after 48 h of incubation even at high concentration (800 μg/mL). Zeta potential values varied with N/P ratio confirming complexation with siRNA. Successful cellular uptake of the star polymers in MC3T3-E1.4 cells was observed by confocal microscopy and flow cytometry after 24 h of incubation.

摘要

星型聚合物具有聚乙二醇(PEG)臂和可降解阳离子核,通过聚乙二醇甲醚甲基丙烯酸酯大分子单体(PEGMA)、2-(二甲氨基)乙基甲基丙烯酸酯(DMAEMA)和二硫代二甲基丙烯酸酯(交联剂,SS)的原子转移自由基共聚(ATRP)合成。星形聚合物的直径约为 15nm,并在氧化还原条件下通过谷胱甘肽处理降解为单个聚合物链,这是由于二硫键交联剂的断裂,这一点通过动态光散射得到了证实。星形聚合物与小鼠颅顶前骨前体细胞(胚胎第 1 天,亚克隆 4(MC3T3-E1.4))一起培养,以确定其生物相容性。数据表明,星形聚合物具有生物相容性,即使在高浓度(800μg/mL)下孵育 48 小时后,细胞存活率仍≥80%。Zeta 电位值随 N/P 比的变化而变化,证实了与 siRNA 的复合物形成。通过共聚焦显微镜和流式细胞术观察到星形聚合物在 MC3T3-E1.4 细胞中的摄取。

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