Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
J Control Release. 2011 Oct 30;155(2):303-11. doi: 10.1016/j.jconrel.2011.07.009. Epub 2011 Jul 14.
Polycations are one of the most frequently used classes of materials for non-viral gene transfer in vivo. Several studies have demonstrated a sensitive relationship between polymer structure and delivery activity. In this work, we used reverse addition-fragmentation chain transfer (RAFT) polymerization to build a panel of N-(2-hydroxypropyl)methacrylamide (HPMA)-oligolysine copolymers with varying peptide length and polymer molecular weight. The panel was screened for optimal DNA-binding, colloidal stability in salt, high transfection efficiency, and low cytotoxicity. Increasing polyplex stability in PBS correlated with increasing polymer molecular weight and decreasing peptide length. Copolymers containing K(5) and K(10) oligocations transfected cultured cells with significantly higher efficiencies than copolymers of K(15). Four HPMA-oligolysine copolymers were identified that met the desired criteria. Polyplexes formed with these copolymers demonstrated both salt stability and transfection efficiencies on-par with poly(ethylenimine) PEI in cultured cells.
聚阳离子是体内非病毒基因转移最常用的材料之一。多项研究表明，聚合物结构与输送活性之间存在敏感关系。在这项工作中，我们使用反向加成-断裂链转移（RAFT）聚合来构建一系列具有不同肽长度和聚合物分子量的 N-（2-羟丙基）甲基丙烯酰胺（HPMA）-寡聚赖氨酸共聚物。该共聚物面板经过筛选，以获得最佳的 DNA 结合能力、盐中的胶体稳定性、高转染效率和低细胞毒性。在 PBS 中增加聚集体的稳定性与增加聚合物分子量和降低肽长度相关。含有 K(5)和 K(10)寡阳离子的共聚物转染培养细胞的效率明显高于 K(15)的共聚物。鉴定出四种符合要求的 HPMA-寡聚赖氨酸共聚物。与培养细胞中的聚（亚乙基亚胺）PEI 相比，这些共聚物形成的聚集体既具有盐稳定性，又具有转染效率。
