Pflueger Iris, Charrat Coralie, Mellet Carmen Ortiz, García Fernández José M, Di Giorgio Christophe, Benito Juan M
Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, Américo Vespucio 49, E-41092 Sevilla, Spain.
Institut de Chimie Nice, UMR 7272, Université de Nice Sophia Antipolis, CNRS, 28, Avenue de Valrose, F-06108 Nice, France.
Org Biomol Chem. 2016 Oct 25;14(42):10037-10049. doi: 10.1039/c6ob01882c.
Exhaustive structure-efficacy relationship studies on nonviral gene delivery systems are often hampered by the ill-defined or polydisperse nature of the formulations. Facial amphiphiles based on rigid cage-type molecular scaffolds offer unique possibilities towards these studies. Taking advantage of regioselective functionalization schemes, we have synthesized a library of cationic cyclodextrin (CD) derivatives combining a range of hydrophilic and lipophilic domains. We have scrutinized how the hydrophilic-lipophilic balance (HLB) around the CD scaffold determines their self-assembly capabilities and the DNA binding and release abilities of the corresponding CD : DNA nanocomplexes (CDplexes). These features have been ultimately correlated with their capabilities to deliver a reporter luciferase-encoding pDNA into COS-7 cells. The ensemble of results demonstrates that fine tuning of the HLB is critical to induce compaction of DNA by the CD-based facial amphiphiles into transfection-productive CDplexes.
对非病毒基因递送系统进行详尽的构效关系研究常常受到制剂定义不明确或多分散性质的阻碍。基于刚性笼型分子支架的表面两亲物为这些研究提供了独特的可能性。利用区域选择性功能化方案，我们合成了一系列阳离子环糊精（CD）衍生物库，这些衍生物结合了一系列亲水性和亲脂性结构域。我们仔细研究了CD支架周围的亲水-亲脂平衡（HLB）如何决定其自组装能力以及相应的CD：DNA纳米复合物（CDplexes）的DNA结合和释放能力。这些特性最终与它们将报告荧光素酶编码pDNA递送至COS-7细胞的能力相关联。结果表明，精细调节HLB对于通过基于CD的表面两亲物将DNA压缩成具有转染活性的CDplexes至关重要。
