Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA.
Biomacromolecules. 2012 Oct 8;13(10):3220-7. doi: 10.1021/bm3009999. Epub 2012 Sep 25.
A series of reducible polycationic copper chelators (RPCs) based on 1,4,8,11-tetraazacyclotetradecane (cyclam) were synthesized by Michael addition. Molecular weight of the polycations was controlled by reaction stoichiometry and reaction conditions, resulting in polymers with molecular weights ranging from 4400 to 13 800. The cyclam moieties in the polycations retained their ability to form complexes with Cu(II). The presence of disulfide bonds in the polycations resulted in substantially lower cytotoxicity than control 25 kDa poly(ethyleneimine). RPC as well as their complexes with Cu(II) exhibited high transfection activity in vitro. The reported polycationic Cu(II) chelates represent promising nucleic acid delivery vectors with potential for future theranostic applications.
一系列基于 1,4,8,11-四氮杂环十四烷（环四胺）的可还原聚阳离子铜螯合物（RPC）通过迈克尔加成法合成。通过反应化学计量和反应条件来控制聚阳离子的分子量，从而得到分子量范围为 4400 至 13800 的聚合物。聚阳离子中环四胺部分保留了与 Cu(II) 形成配合物的能力。聚阳离子中存在二硫键，其细胞毒性明显低于对照的 25 kDa 聚（亚乙基亚胺）。RPC 及其与 Cu(II) 的配合物在体外表现出很高的转染活性。所报道的聚阳离子 Cu(II) 螯合物具有作为核酸传递载体的潜力，有望用于未来的治疗诊断应用。
