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T807-modified human serum albumin biomimetic nanoparticles for targeted drug delivery across the blood-brain barrier.
Journal of Drug Targeting ( IF 4.3 ) Pub Date : 2020-07-14 , DOI: 10.1080/1061186x.2020.1777420
Chunhong Gao 1 , Wei Gong 1 , Meiyan Yang 1 , Xiaoyang Chu 2 , Yuli Wang 1 , Zhiping Li 1 , Yang Yang 1 , Chunsheng Gao 1
Affiliation  

Abstract

Novel biocompatible Human Serum Albumin (HSA) nanoparticles composed of membrane of erythrocytes (ETm)-coated and DSPE-PEG3400-T807 segments have been designed for sustained drug delivery across the blood–brain barrier (BBB). The nanoparticles have developed by induced albumin self-assembly with glutathione as reducing agent. The chemical, physical and biocompatible properties of the T807/ETm-HSA nanoparticles have been characterised by hydrogen nuclear magnetic resonance, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, transmission electron microscopy, dynamic light scattering and confocal laser scanning microscopy techniques. The unique targeting properties of the nanoparticles after fabrication with the brain-targeted ligand T807 was demonstrated by their attaching to brain cells as well as their enhanced transport ability to cross the BBB. In a further demonstration of their ability to target brain cells, in vivo living imaging revealed that T807/ETm-HSA nanoparticles accumulated in the mice brain after intravenous injection. The surface modification of ETm/HSA nanoparticles with the brain-targeted T807 demonstrated in this work represents a highly novel and effective strategy to provide efficient brain targeting and shows promise for the future in using modified ETm-coated HSA nanoparticles to penetrate the brain.



中文翻译:

T807 修饰的人血清白蛋白仿生纳米粒子,用于跨血脑屏障靶向药物递送。

摘要

由红细胞膜 (ETm) 和 DSPE-PEG 3400组成的新型生物相容性人血清白蛋白 (HSA) 纳米粒子-T807 片段设计用于跨血脑屏障 (BBB) 的持续药物递送。纳米粒子是通过诱导白蛋白自组装与谷胱甘肽作为还原剂而开发的。T807/ETm-HSA 纳米粒子的化学、物理和生物相容性特性已通过氢核磁共振、基质辅助激光解吸/电离飞行时间质谱、透射电子显微镜、动态光散射和共聚焦激光扫描表征显微技术。用脑靶向配体 T807 制造后的纳米颗粒的独特靶向特性通过它们与脑细胞的附着以及它们穿过 BBB 的增强运输能力得到证明。为了进一步证明它们在体内靶向脑细胞的能力活体成像显示 T807/ETm-HSA 纳米颗粒在静脉注射后在小鼠大脑中积累。在这项工作中展示的 ETm/HSA 纳米粒子与大脑靶向 T807 的表面改性代表了一种高度新颖和有效的策略,可提供有效的大脑靶向,并显示出使用改性 ETm 涂层 HSA 纳米粒子穿透大脑的未来前景。

更新日期:2020-07-14
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