Comparison of four different peptides to enhance accumulation of liposomes into the brain
Comparison of four different peptides to enhance accumulation of liposomes into the brain
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四种不同肽增强脂质体在大脑中积累的比较
DOI：
10.3109/1061186x.2011.639022
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发表时间：
2012-04-01
影响因子：
4.5
通讯作者：
He, Qin
中科院分区：
文献类型：
--
作者：
Qin, Yao;Zhang, Qianyu;He, Qin
细胞穿透肽达特似乎可以迅速进入细胞，可以有效地穿过血脑屏障。它已被确定为增强脂质体的脑递送。然而，人们对其机制知之甚少。达特含有由六个精氨酸和两个赖氨酸残基组成的碱性区域。这八种基本氨基酸似乎是其高效膜转运和脑递送的关键。在这项研究中，四个选定的肽合成。(1)末端为半胱氨酸的达特肽（Cys-AYGRKKRRQRRR）。(2)具有无序序列的达特肽（Cys-RKARYRGRKRQR）。(3)甘氨酸和谷氨酸取代的达特肽（Cys-AYGGQQGGQGGG）。(4)R8（Cys-RRRRRRR）。选择脂质体作为递送载体。肽与脂质体共价键合。我们比较了四种肽的脑靶向潜力，并研究了它们在体外和体内将脂质体靶向脑的能力。探讨了大鼠脑毛细血管内皮细胞（BCECs）和C6细胞对这4种脂质体的摄取情况及其内吞途径的机制。还定性和定量地研究了体内生物分布。结果表明，多肽的电荷在增强其脑内释放中起重要作用。该序列与其膜转位和脑递送关系不大，表明达特肽可能没有特异性受体或转运蛋白。
The cell penetrating peptide TAT, which appears to enter cells with alacrity, can pass through the BBB efficiently. It has been indentified to enhance the brain delivery of the liposome. However, little was known about its mechanism. TAT contains a basic region consisting of six arginine and two lysine residues. These eight basic amino acids seem to be the key to its highly efficient membrane translocation and brain delivery. In this study, four selected peptides are synthesized. (1) TAT peptide with terminal Cysteine (Cys-AYGRKKRRQRRR). (2) TAT peptide with disordered sequence (Cys-RKARYRGRKRQR). (3) Glycine and glutamic acid substituted TAT peptide (Cys-AYGGQQGGQGGG). (4) R8 (Cys-RRRRRRRR). Liposomes were chosen as the delivery vehicle. The peptide was covalently bonded with the liposome. We compare four peptides for their brain targeting potential, and investigate their ability to target liposomes to the brain in vitro and in vivo. The cellular uptake of these four liposomes by brain capillary endothelial cells (BCECs) of rats and C6s and the mechanism of the pathway of endocytosis were explored. Biodistribution in vivo was also investigated qualitatively and quantitatively. The results showed that the charge of the peptide played an important role in enhancing its brain delivery. The sequence had little to do with its membrane translocation and brain delivery indicated there might be no specific receptor or transporter for the Tat peptide.