Network of Excellence for Functional Biomaterials, National University of Ireland, Galway, Ireland.
J Am Chem Soc. 2012 Mar 14;134(10):4782-9. doi: 10.1021/ja2105575. Epub 2012 Mar 1.
The large research effort focused on enhancing nonviral transfection vectors has clearly demonstrated that their macromolecular structure has a significant effect on their transfection efficacy. The 3D branched polymeric structures, such as dendrimers, have proved to be a very effective structure for polymeric transfection vectors; however, so far the dendritic polymers have not delivered on their promise. This is largely because a wide range of dendritic polymer materials with tailored multifunctional properties and biocompatibility required for such applications are not yet accessible by current routes. Herein, we report the design and synthesis of new 3D "Single Cyclized" polymeric gene vectors with well-defined compositions and functionalities via a one-step synthesis from readily available vinyl monomers. We observe that this polymer structure of a single chain linked to itself interacts differently with plasmid DNA compared to conventional vectors and when tested over a range of cell types, has a superior transfection profile in terms of both luciferase transfection capability and preservation of cell viability. This new knotted structure shows high potential for gene delivery applications through a combination of simplicity in synthesis, scalability, and high performance.
研究人员投入大量精力来改进非病毒转染载体，这清楚地表明它们的大分子结构对转染效率有重大影响。3D 支化聚合物结构，如树枝状聚合物，已被证明是一种非常有效的聚合物转染载体结构；然而，迄今为止，树枝状聚合物尚未实现其承诺。这在很大程度上是因为，目前还无法通过现有途径获得适用于此类应用的、具有定制多功能特性和生物相容性的各种树枝状聚合物材料。在此，我们报告了一种新型 3D“单环化”聚合物基因载体的设计和合成，该载体通过一步合成，由易得的乙烯基单体合成而来，具有明确的组成和功能。我们观察到，与传统载体相比，这种自身连接的单链聚合物结构与质粒 DNA 的相互作用方式不同，并且在一系列细胞类型中进行测试时，在荧光素酶转染能力和细胞活力保持方面均具有优越的转染谱。这种新的纽结结构通过合成的简单性、可扩展性和高性能相结合，显示出在基因传递应用方面的巨大潜力。
