阳离子树状聚合物与肌动蛋白的两相相互作用。
Biphasic interactions between a cationic dendrimer and actin.
机构信息
Centre for Drug Delivery Research (CDDR), The School of Pharmacy, University of London, London, UK.
出版信息
J Drug Target. 2010 Dec;18(10):803-11. doi: 10.3109/1061186X.2010.521159. Epub 2010 Oct 11.
Gene delivery systems face the problem not only of the route toward the cell and tissues in question, but also of the molecularly crowded environment of both the cytoplasm and the nucleus itself. One of the physical barriers in the cytoplasm for diffusing nanoparticles is an actin network. Here, we describe the finding that a self-fluorescent sixth generation cationic dendrimer (6 nm in diameter) interacts reversibly and possibly electrostatically with actin filaments in vitro. Not only does this interaction slow the diffusion of the dendrimer but it also affects actin polymerization in a biphasic manner. At low concentrations the dendrimer behaves like a G-binding actin protein, retarding actin polymerization, whereas at high concentrations the dendrimer acts as a nucleating protein accelerating the polymerization. Thus in vivo the diffusion of a dendrimer carrier such as this has both physical and chemical elements: by decreasing polymerization it might accelerate its own transport, and by enhancing actin polymerization retard it. This finding suggests that such a dendrimer may have a role as an anticancer agent through its inhibitory effect on actin polymerization.
基因传递系统不仅面临着进入目标细胞和组织的途径问题,还面临着细胞质和细胞核自身分子拥挤环境的问题。在细胞质中,扩散纳米颗粒的物理障碍之一是肌动蛋白网络。在这里,我们描述了一种自发荧光的第六代阳离子树状大分子(直径 6nm)与体外肌动蛋白丝可逆且可能静电相互作用的发现。这种相互作用不仅减缓了树状大分子的扩散,而且还以双相方式影响肌动蛋白聚合。在低浓度下,树状大分子表现为与 G 结合的肌动蛋白蛋白,从而减缓肌动蛋白聚合,而在高浓度下,树状大分子充当成核蛋白加速聚合。因此,在体内,这种树突状聚合物载体的扩散具有物理和化学双重作用:通过降低聚合作用,它可能会加速自身的运输,而通过增强肌动蛋白聚合作用来减缓运输。这一发现表明,这种树突状聚合物可能通过抑制肌动蛋白聚合而发挥抗癌作用。