Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China.
ACS Nano. 2012 Apr 24;6(4):3304-10. doi: 10.1021/nn300240p. Epub 2012 Mar 29.
A brain delivery probe was prepared by covalently conjugating lactoferrin (Lf) to a poly(ethylene glycol) (PEG)-coated Fe(3)O(4) nanoparticle in order to facilitate the transport of the nanoparticles across the blood-brain barrier (BBB) by receptor-mediated transcytosis via the Lf receptor present on cerebral endothelial cells. The efficacy of the Fe(3)O(4)-Lf conjugate to cross the BBB was evaluated in vitro using a cell culture model for the blood-brain barrier as well as in vivo in SD rats. For an in vitro experiment, a well-established porcine BBB model was used based on the primary culture of cerebral capillary endothelial cells grown on filter supports, thus allowing one to follow the transfer of nanoparticles from the apical (blood) to the basolateral (brain) side. For in vivo experiments, SD rats were used as animal model to detect the passage of the nanoparticles through the BBB by MRI techniques. The results of both in vitro and in vivo experiments revealed that the Fe(3)O(4)-Lf probe exhibited an enhanced ability to cross the BBB in comparison to the PEG-coated Fe(3)O(4) nanoparticles and further suggested that the Lf-receptor-mediated transcytosis was an effective measure for delivering the nanoparticles across the BBB.
为了通过脑内皮细胞上的乳铁蛋白受体介导的胞吞作用促进纳米颗粒穿过血脑屏障（BBB），将乳铁蛋白（Lf）共价偶联到聚乙二醇（PEG）包覆的 Fe(3)O(4)纳米颗粒上，制备了脑内递药探针。使用基于在过滤器支持物上生长的脑毛细血管内皮细胞的原代培养的成熟猪 BBB 模型，在体外评估了 Fe(3)O(4)-Lf 缀合物穿过 BBB 的功效，以及在 SD 大鼠体内的功效。对于体内实验，使用 SD 大鼠作为动物模型，通过 MRI 技术检测纳米颗粒穿过 BBB 的情况。体外和体内实验的结果均表明，与 PEG 包覆的 Fe(3)O(4)纳米颗粒相比，Fe(3)O(4)-Lf 探针具有增强的穿过 BBB 的能力，并且进一步表明乳铁蛋白受体介导的胞吞作用是将纳米颗粒穿过 BBB 的有效手段。
