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Pendant Polymer:Amino-β-Cyclodextrin:siRNA Guest:Host Nanoparticles as Efficient Vectors for Gene Silencing
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2012-04-30 , DOI: 10.1021/ja300690j
Aditya Kulkarni 1 , Kyle DeFrees , Seok-Hee Hyun , David H Thompson
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2012-04-30 , DOI: 10.1021/ja300690j
Aditya Kulkarni 1 , Kyle DeFrees , Seok-Hee Hyun , David H Thompson
Affiliation
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A novel siRNA delivery vector has been developed, based on the self-assembly of monosubstituted cationic β-CD derivatives with a poly(vinyl alcohol)MW27kD (PVA) main-chain polymer bearing poly(ethylene glycol)MW2000 (PEG) and acid-labile cholesterol-modified (Chol) grafts through an acid-sensitive benzylidene acetal linkage. These components were investigated for their ability to form nanoparticles with siRNA using two different assembly schemes, involving either precomplexation of the pendant Chol-PVA-PEG polymer with the cationic β-CD derivatives before siRNA condensation or siRNA condensation with the cationic β-CD derivatives prior to addition of Chol-PVA-PEG to engage host:guest complexation. The pendant polymer:amino-β-CD:siRNA complexes were shown to form nanoparticles in the size range of 120-170 nm, with a slightly negative zeta potential. Cell viability studies in CHO-GFP cells shows that these materials have 10(3)-fold lower cytotoxicities than 25 kD bPEI, while maintaining gene-silencing efficiencies that are comparable to those of benchmark transfection reagents such as bPEI and Lipofectamine 2000. These results suggest that the degradable Chol-PVA-PEG polymer is able to self-assemble in the presence of siRNA and cationic-β-CD to form nanoparticles that are an effective and low-toxicity vehicle for delivering siRNA cargo to target cells.
中文翻译：
悬垂聚合物：氨基-β-环糊精：siRNA 客体：宿主纳米颗粒作为基因沉默的有效载体
基于单取代阳离子 β-CD 衍生物与聚（乙烯醇）MW27kD（PVA）主链聚合物（带有聚（乙二醇）MW2000（PEG）和酸-不稳定的胆固醇改性（Chol）通过酸敏感的亚苄基缩醛键接枝。使用两种不同的组装方案研究了这些成分与 siRNA 形成纳米颗粒的能力，包括在 siRNA 缩合之前预复合 Chol-PVA-PEG 聚合物与阳离子 β-CD 衍生物或 siRNA 与阳离子 β-CD 衍生物的缩合在添加 Chol-PVA-PEG 以进行宿主：客体复合之前。悬垂聚合物：氨基-β-CD：siRNA 复合物显示出形成尺寸范围为 120-170 nm 的纳米颗粒，具有略微负的 zeta 电位。
更新日期：2012-04-30
中文翻译：
悬垂聚合物：氨基-β-环糊精：siRNA 客体：宿主纳米颗粒作为基因沉默的有效载体
基于单取代阳离子 β-CD 衍生物与聚（乙烯醇）MW27kD（PVA）主链聚合物（带有聚（乙二醇）MW2000（PEG）和酸-不稳定的胆固醇改性（Chol）通过酸敏感的亚苄基缩醛键接枝。使用两种不同的组装方案研究了这些成分与 siRNA 形成纳米颗粒的能力，包括在 siRNA 缩合之前预复合 Chol-PVA-PEG 聚合物与阳离子 β-CD 衍生物或 siRNA 与阳离子 β-CD 衍生物的缩合在添加 Chol-PVA-PEG 以进行宿主：客体复合之前。悬垂聚合物：氨基-β-CD：siRNA 复合物显示出形成尺寸范围为 120-170 nm 的纳米颗粒，具有略微负的 zeta 电位。
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