T807-modified human serum albumin biomimetic nanoparticles for targeted drug delivery across the blood-brain barrier

J Drug Target. 2020 Dec;28(10):1085-1095. doi: 10.1080/1061186X.2020.1777420. Epub 2020 Jul 14.

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.

Keywords: Blood–brain barrier; T807; biomimetic nanoparticles; drug delivery; human serum albumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomimetics
  • Blood-Brain Barrier / metabolism*
  • Carbolines / pharmacokinetics*
  • Cell Survival
  • Chemistry, Pharmaceutical
  • Drug Carriers / chemistry
  • Endothelial Cells
  • Erythrocyte Membrane / metabolism*
  • Mice
  • Nanoparticles / chemistry*
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Serum Albumin, Human / chemistry*

Substances

  • Carbolines
  • Drug Carriers
  • Phosphatidylethanolamines
  • 1,2-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
  • Serum Albumin, Human