Brain-targeting mechanisms of lactoferrin-modified DNA-loaded nanoparticles
Brain-targeting mechanisms of lactoferrin-modified DNA-loaded nanoparticles
复制标题
DOI：
10.1038/jcbfm.2009.104
复制
发表时间：
2009-12-01
影响因子：
6.3
通讯作者：
Pei, Yuanying
中科院分区：
文献类型：
--
作者：
Huang, Rongqin;Ke, Weilun;Pei, Yuanying
配体介导的脑靶向给药是目前研究的热点之一。阐明确切的靶向机制有助于有效地设计这些药物递送系统。在我们以前的研究中，乳铁蛋白（Lf）被成功地利用作为脑靶向配体来修饰阳离子树枝状聚合物基纳米颗粒（NPs）。本研究首次系统研究了LF修饰纳米粒对脑组织的作用机制。脑毛细血管内皮细胞（BCECs）对LF修饰的载体和NP的摄取与网格蛋白依赖的内吞作用、小窝介导的内吞作用和巨胞饮作用有关。胞内转运结果表明，LF修饰的NPs可以在5分钟内迅速进入酸性内溶酶体区室，然后在30分钟内部分逃逸。LF修饰的载体和纳米颗粒都显示出比未修饰的载体更高的血脑屏障穿越效率。所有的结果表明，受体和吸附介导的机制有助于LF修饰的载体和NP的细胞摄取。通过高分子聚合物与配体的协同作用，可以实现增强的脑靶向给药。脑血流与代谢杂志（2009）29，1914-1923; doi：10.1038/jcbfm.2009.104; 2009年8月5日在线发表
Ligand-mediated brain-targeting drug delivery is one of the focuses at present. Elucidation of exact targeting mechanisms serves to efficiently design these drug delivery systems. In our previous studies, lactoferrin (Lf) was successfully exploited as a brain-targeting ligand to modify cationic dendrimer-based nanoparticles (NPs). The mechanisms of Lf-modified NPs to the brain were systematically investigated in this study for the first time. The uptake of Lf-modified vectors and NPs by brain capillary endothelial cells (BCECs) was related to clathrin-dependent endocytosis, caveolae-mediated endocytosis, and macropinocytosis. The intracellular trafficking results showed that Lf-modified NPs could rapidly enter the acidic endolysosomal compartments within 5 mins and then partly escape within 30 mins. Both Lf-modified vectors and NPs showed higher blood-brain barrier-crossing efficiency than unmodified counterparts. All the results suggest that both receptor- and adsorptive-mediated mechanisms contribute to the cellular uptake of Lf-modified vectors and NPs. Enhanced brain-targeting delivery could be achieved through the synergistic effect of the macromolecular polymers and the ligand. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1914-1923; doi:10.1038/jcbfm.2009.104; published online 5 August 2009