Effects of trehalose click polymer length on pDNA complex stability and delivery efficacy
Effects of trehalose click polymer length on pDNA complex stability and delivery efficacy
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DOI：
10.1016/j.biomaterials.2007.01.037
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发表时间：
2007-06-01
期刊：
影响因子：
14
通讯作者：
Reineke, Theresa M.
中科院分区：
文献类型：
--
作者：
Srinivasachari, Sathya;Liu, Yemin;Reineke, Theresa M.
目前正研究阳离子聚合物作为非病毒载体将治疗性DNA递送到细胞中。在这项研究中，一系列的海藻糖为基础的含四个仲胺的重复单元的糖共聚物通过“点击反应”[聚合度（n（w））= 35，53，75，或100]，以阐明如何聚合物的长度影响的生物活性合成。通过凝胶电泳、肝素竞争性置换和等温滴定量热分析确定，这四种结构以相似的亲和力结合并电荷中和pDNA，且与长度无关。动态光散射测量表明，形成的聚合物与较长的聚合物（n（w）= 53，75，或100）抑制在含有血清的介质中的絮凝，而形成的聚合物与较短的聚合物（n（w）= 35）迅速聚集。通过透射电子显微镜研究观察到类似的结果，其中用具有较长聚合度的聚合物形成的纳米颗粒在含有10%血清的介质中显示离散颗粒。转染实验表明，聚合物在低NIP比率下表现出低细胞毒性，并且可以促进HeLa和H9 c2（2-1）细胞中的高细胞摄取和基因表达，并且结果取决于聚合度（较长的聚合物产生较高的转染和毒性）。(C)2007爱思唯尔有限公司保留所有权利。
Cationic polymers are currently being studied as non-viral vectors to deliver therapeutic DNA into cells. In this study, a series of trehalose-based glycopolymers containing four secondary amines in the repeat unit were synthesized via the 'click reaction' [degrees of polymerization (n(w)) = 35, 53, 75, or 100] to elucidate how the polymer length affects the bioactivity. The four structures bound and charge-neutralized pDNA with similar affinity that was independent of the length, as determined through gel electrophoresis, heparin competitive displacement, and isothermal titration calorimetric assays. Dynamic light scattering measurements revealed that the polyplexes formed with the longer polymers (n(w) = 53, 75, or 100) inhibited flocculation in media containing serum, whereas the polyplexes formed with the shorter polymer (n(w) = 35) aggregated rapidly. Similar results were observed via transmission electron microscopy studies, where the nanoparticles formed with the polymers having longer degrees of polymerization showed discrete particles in media containing 10% serum. Transfection experiments revealed that the polymers exhibited low cytotoxicity at low NIP ratios and could facilitate high cellular uptake and gene expression in HeLa and H9c2(2-1) cells, and the results were dependent on the degrees of polymerization (longer polymers yielded higher transfection and toxicity). (C) 2007 Elsevier Ltd. All rights reserved.