Department of Chemistry, Carnegie Mellon University , 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States.
Biomacromolecules. 2015 Jan 12;16(1):236-45. doi: 10.1021/bm501449a. Epub 2014 Dec 17.
The field of RNA interference depends on the development of safe and efficient carriers for short interfering ribonucleic acid (siRNA) delivery. Conventional cationic monomers for siRNA delivery have utilized the nitrogen heteroatom to produce cationic charges. Here, we polymerized cationic sulfonium (meth)acrylate by activators regenerated by electron transfer (ARGET) atom transfer radical polymerization (ATRP) to form polymers with narrow molecular weight distributions for siRNA delivery. The tertiary sulfonium species was stable toward dealkylation in water but less stable in the polar aprotic solvent dimethyl sulfoxide. Block copolymers poly(ethylene oxide) with poly(meth)acrylate containing sulfonium moieties were prepared as an siRNA delivery platform. Results suggested block copolymers were biocompatible up to 50 μg/mL in vitro and formed polyplexes with siRNA. Additionally, block copolymers protected siRNAs against endonuclease digestion and facilitated knockdown of glyceraldehyde 3-phosphate dehydrogenase (Gapdh) mRNA expression in murine calvarial preosteoblasts. The versatility, biocompatibility, and cationic nature of these tertiary sulfonium groups are expected to find widespread biological applications.
RNA 干扰领域依赖于安全有效的短干扰核糖核酸 (siRNA) 传递载体的发展。传统的用于 siRNA 传递的阳离子单体利用氮杂原子产生阳离子电荷。在这里，我们通过电子转移 (ARGET) 原子转移自由基聚合 (ATRP) 聚合阳离子锍 (甲基) 丙烯酸酯，形成具有窄分子量分布的聚合物，用于 siRNA 传递。叔锍物种在水中对脱烷基化稳定，但在极性非质子溶剂二甲基亚砜中稳定性较差。含锍部分的聚 (甲基) 丙烯酸酯与聚氧乙烯的嵌段共聚物被制备为 siRNA 传递平台。结果表明，嵌段共聚物在体外高达 50 μg/mL 时具有生物相容性，并与 siRNA 形成聚集体。此外，嵌段共聚物保护 siRNA 免受核酸内切酶的消化，并有助于降低鼠颅骨前成骨细胞中甘油醛 3-磷酸脱氢酶 (Gapdh) mRNA 的表达。这些叔锍基团的多功能性、生物相容性和阳离子性质有望在广泛的生物学应用中找到。
