Huang Rong-qin, Ke Wei-lun, Qu Ying-hua, Zhu Jian-hua, Pei Yuan-ying, Jiang Chen
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
J Biomed Sci. 2007 Jan;14(1):121-8. doi: 10.1007/s11373-006-9121-7. Epub 2006 Oct 18.
We present, herein, the evidence for lactoferrin (Lf) binding sites in brain endothelial capillary cells (BCECs) and mouse brain. The results from confocal microscopy showed the presence of Lf receptors on the surface of BCECs and the receptor-mediated endocytosis for Lf to enter the cells. Saturation binding analyses revealed that Lf receptors exhibited two classes of binding sites in BCECs (high affinity: dissociation constant (K (d)) = 6.77 nM, binding site density (B (max)) = 10.3 fmol bound/mug protein; low affinity: K (d) = 4815 nM, B (max) = 1190 fmol bound/mug protein) and membrane preparations of mouse brain (high affinity: K (d) = 10.61 nM, B (max) = 410 fmol bound/mug protein; low affinity: K (d) = 2228 nM, B (max) = 51641 fmol bound/mug protein). The distribution study indicated the effective uptake of (125)I-Lf in brain after intravenous administration. The present study provides experimental evidence for the application of Lf as a novel ligand for brain targeting.
在此，我们展示了乳铁蛋白（Lf）在脑内皮毛细血管细胞（BCECs）和小鼠脑中结合位点的证据。共聚焦显微镜检查结果显示，BCECs表面存在Lf受体，且Lf通过受体介导的内吞作用进入细胞。饱和结合分析表明，Lf受体在BCECs中表现出两类结合位点（高亲和力：解离常数（K (d)） = 6.77 nM，结合位点密度（B (max)） = 10.3 fmol结合/微克蛋白质；低亲和力：K (d) = 4815 nM，B (max) = 1190 fmol结合/微克蛋白质）以及小鼠脑的膜制剂中（高亲和力：K (d) = 10.61 nM，B (max) = 410 fmol结合/微克蛋白质；低亲和力：K (d) = 2228 nM，B (max) = 51641 fmol结合/微克蛋白质）。分布研究表明静脉注射后脑中有效摄取了(125)I-Lf。本研究为Lf作为脑靶向新配体的应用提供了实验证据。
