Department of Chemistry, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
J Control Release. 2011 Oct 10;155(1):18-25. doi: 10.1016/j.jconrel.2010.08.011. Epub 2010 Aug 25.
The work demonstrated the successful delivery of gene to mouse brain overcoming the blood-brain barrier (BBB) through expedient vector construct having RVG peptide as targeting ligand for neuronal cells. The newly developed delivery vector was designed to impart bioreducibility for greater intracellular pDNA release, higher serum stability and efficient complexing ability by incorporating disulfide linkage, PEG and low molecular weight polyethylenimine, respectively. The physiochemical properties of the polyplex, its cytotoxicity and the in vitro transfection efficiency on Neuro2a cell were studied prior to the successful in vivo study. In vivo fluorescence assay substantiated the permeation of the pDNA loaded polymeric vector through the BBB. The RVG-mediated target-specific cellular uptake of polymeric vector was established conclusively by competitive assay.
该工作展示了通过具有 RVG 肽作为神经细胞靶向配体的便捷载体构建，成功地将基因递送到克服血脑屏障 (BBB) 的小鼠大脑中。新开发的递送载体旨在通过分别引入二硫键、PEG 和低分子量聚乙烯亚胺来赋予生物还原性，以实现更大的细胞内 pDNA 释放、更高的血清稳定性和更高的有效结合能力。在成功进行体内研究之前，研究了多聚物的物理化学性质、细胞毒性以及对 Neuro2a 细胞的体外转染效率。体内荧光测定证实了负载 pDNA 的聚合物载体通过血脑屏障的渗透。通过竞争测定，确定了 RVG 介导的聚合物载体的靶特异性细胞摄取。
