Perumal Omathanu P, Inapagolla Rajyalakshmi, Kannan Sujatha, Kannan Rangaramanujam M
Critical Care Medicine, Children's Hospital of Michigan, Wayne State University, Detroit, MI 48201, USA.
Biomaterials. 2008 Aug-Sep;29(24-25):3469-76. doi: 10.1016/j.biomaterials.2008.04.038. Epub 2008 May 22.
Dendrimers are an emerging group of nanostructured, polymeric biomaterials that have potential as non-viral vehicles for delivering drugs and genetic material to intracellular targets. They have a high charge density with tunable surface functional groups, which can alter the local environment and influence cellular interactions. This can have a significant impact on the intracellular trafficking of dendrimer-based nanodevices. With the help of flow cytometry, fluorescence microscopy, and by using specific inhibitors, the influence of surface functionality on their uptake in A549 lung epithelial cells, and subsequent intracellular distribution was investigated. In this paper, we have shown that even though all the dendrimers are taken up by fluid-phase endocytosis, significant differences in uptake mechanisms exist. Anionic dendrimers appear to be mainly taken up by caveolae mediated endocytosis in A549 lung epithelial cells, while cationic and neutral dendrimers appear to be taken in by a non-clathrin, non-caveolae mediated mechanism that may be by electrostatic interactions or other non-specific fluid-phase endocytosis. These findings open up new possibilities of targeting therapeutic agents to specific cell organelles based on surface charge.
树枝状大分子是一类新兴的纳米结构聚合物生物材料，有潜力作为非病毒载体将药物和遗传物质递送至细胞内靶点。它们具有高电荷密度和可调节的表面官能团，这可以改变局部环境并影响细胞相互作用。这可能会对基于树枝状大分子的纳米器件的细胞内运输产生重大影响。借助流式细胞术、荧光显微镜，并使用特定抑制剂，研究了表面官能团对其在A549肺上皮细胞中的摄取以及随后细胞内分布的影响。在本文中，我们已经表明，尽管所有树枝状大分子都是通过液相内吞作用被摄取的，但摄取机制存在显著差异。阴离子树枝状大分子在A549肺上皮细胞中似乎主要通过小窝介导的内吞作用被摄取，而阳离子和中性树枝状大分子似乎是通过一种非网格蛋白、非小窝介导的机制被摄取，这种机制可能是通过静电相互作用或其他非特异性液相内吞作用。这些发现为基于表面电荷将治疗剂靶向特定细胞器开辟了新的可能性。
