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Evaluation of the cell-penetrating peptide TAT as a trans-blood-brain barrier delivery vehicle

机译:评估细胞穿透肽TAT作为跨血脑屏障递送载体

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Therapeutic delivery into the brain parenchyma is difficult due to the presence of the blood-brain barrier (BBB). One potential solution is to use cell-penetrating peptides (CPPs). CPPs are short peptides made up of primarily positively charged amino acids that have the ability to transduce cell membranes and deliver cargoes to cells. It is unclear, however, whether CPPs can penetrate cell barriers, such as the BBB, and deliver cargoes into cells on the other side. In this study, we examined the ability of the CPP TAT to deliver a green fluorescent protein (GFP) cargo across an endothelial monolayer. GFP-TAT had only minimal permeability across the monolayer, and the rate was no different from GFP alone or other similarly sized dextrans. Furthermore, this permeability was too small to detect transduction of GFP-TAT into astrocytes on the other side of the monolayer. We conclude that TAT does not have the ability to deliver cargoes across an intact BBB, and therefore may not be a suitable vehicle for therapeutic delivery to the brain.
机译:由于存在血脑屏障(BBB),很难将治疗性药物输送到脑实质中。一种潜在的解决方案是使用细胞穿透肽(CPP)。 CPP是由主要带正电荷的氨基酸组成的短肽,具有转导细胞膜并将货物运送到细胞的能力。但是,尚不清楚CPP是否能够穿透细胞屏障,例如血脑屏障,并将货物运送到另一侧的细胞中。在这项研究中,我们检查了CPP TAT跨内皮单层递送绿色荧光蛋白(GFP)货物的能力。 GFP-TAT的单层渗透性极低,其速率与单独的GFP或其他类似大小的葡聚糖没有什么不同。此外,该渗透性太小,无法检测到GFP-TAT向单层另一侧星形胶质细胞的转导。我们得出的结论是,TAT没有能力将货物运送通过完整的BBB,因此可能不是治疗性运送到大脑的合适工具。

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