Department of Energy, Environmental and Chemical Engineering of Washington University in St. Louis, St. Louis, MO 63130, USA.
IEEE Trans Nanobioscience. 2012 Mar;11(1):54-61. doi: 10.1109/TNB.2011.2179555. Epub 2011 Dec 14.
RGD peptides have been incorporated into several gene delivery vehicles to enhance specific interactions of nonviral vehicles with the cell surface. However, there are contradictory results regarding the effect of linear RGD peptides on specific cell surface binding of polyethylene glycol (PEG)-conjugated gene delivery vehicles. This study sought to understand how coupling RGD peptides to PEG vehicles affects cell binding and internalization using a novel four arm PEG backbone. Coupling multiple RGD peptides to the PEG backbone increased the affinity of the vehicle for the cell surface, and that the PEG backbone did not reduce the affinity of RGD peptides for integrin receptors in both kinetic and equilibrium studies. Kinetic studies suggest that cellular internalization of PEG-based vehicles is not regulated by the RGD peptides on the vehicle, but rather by nonspecific interactions with heparan sulfate proteoglycans either alone or in combination with integrins. These results suggest that while increasing the number of RGD peptides per vehicle increases cell binding, but it does not contribute to increased internalization or transfection efficiency.
RGD 肽已被整合到几种基因传递载体中，以增强非病毒载体与细胞表面的特定相互作用。然而，关于线性 RGD 肽对聚乙二醇（PEG）缀合基因传递载体与特定细胞表面结合的影响，存在相互矛盾的结果。本研究旨在使用新型四臂 PEG 骨架，了解将 RGD 肽偶联到 PEG 载体如何影响细胞结合和内化。将多个 RGD 肽偶联到 PEG 骨架上增加了载体与细胞表面的亲和力，并且在动力学和平衡研究中，PEG 骨架并没有降低 RGD 肽与整合素受体的亲和力。动力学研究表明，基于 PEG 的载体的细胞内化不受载体上 RGD 肽的调节，而是通过与硫酸乙酰肝素蛋白聚糖的非特异性相互作用，无论是单独作用还是与整合素结合作用来调节。这些结果表明，虽然每辆载体上增加 RGD 肽的数量会增加细胞结合，但不会导致内化或转染效率的提高。
