摘要
血脑屏障(BBB)由脑毛细血管内皮细胞构成,可以阻止一些药物分子进入大脑,尤其是亲水性分子。像纳米粒子一样的先进分子载体都有允许治疗性蛋白和遗传分子进入中枢神经系统(CNS)的潜力。采用靶向技术,配体或者单克隆分子与脑毛细血管内皮细胞腔面表达的亲和蛋白偶联,纳米粒子可以设计成能够通过脑内皮细胞,或者甚至可以透过内皮细胞导致从血液向脑内转运。目前,抗转铁蛋白受体的结合铁转运蛋白或抗体显示为在血脑屏障中最可行的分子靶向目标。这篇文章综述了脑毛细血管内皮细胞的纳米粒子强化材料,纳米粒子也许通过脑内皮细胞进入和转运,及由脑毛细血管基底膜构成的胞外蛋白三维网状结构是如何抑制;挑战了包裹的纳米粒子大分子是如何通过血脑屏障进行转运的可能性。
关键词: 基膜,血脑屏障,胞吞作用,纳米粒子,神经退行性变,OX26,转胞吞作用,转铁蛋白
Current Medicinal Chemistry
Title:Accessing Targeted Nanoparticles to the Brain: The Vascular Route
Volume: 21 Issue: 36
Author(s): A. Burkhart, M. Azizi, M.S. Thomsen, L.B. Thomsen and T. Moos
Affiliation:
关键词: 基膜,血脑屏障,胞吞作用,纳米粒子,神经退行性变,OX26,转胞吞作用,转铁蛋白
摘要: The blood-brain barrier (BBB), formed by brain capillary endothelial cells, prevents the entry of several drug molecules to the brain, especially molecules hydrophilic in nature. Advanced drug carriers like nanoparticles share the potential to allow entry of therapeutic proteins and genetic molecules into the central nervous system (CNS). Taking a targeting approach by conjugating molecules acting as ligands or monoclonal antibodies with affinity for proteins expressed on the luminal side of brain capillary endothelial cells, the nanoparticles can be designed to enable transport into the brain endothelium, or perhaps even through the endothelium leading to blood to brain transport. Currently, the iron-binding protein transferrin or antibodies raised against the transferrin receptor denote the most feasible molecule for targeting purposes at the BBB. This manuscript reviews the targetability of nanoparticles to the brain capillary endothelial cells, how nanocarriers may enter and transfer through the brain endothelium, and how likely restraints denoted by the threedimensional mesh of the extracellular proteins forming the brain capillary basement membrane challenge the possibilities for enabling transport of large molecules through the BBB encapsulated in nanoparticles.
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Cite this article as:
Burkhart A., Azizi M., Thomsen M.S., Thomsen L.B. and Moos T., Accessing Targeted Nanoparticles to the Brain: The Vascular Route, Current Medicinal Chemistry 2014; 21 (36) . https://dx.doi.org/10.2174/0929867321666140716095317
DOI https://dx.doi.org/10.2174/0929867321666140716095317 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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