Length of surface PEG modulates nanocarrier transcytosis across brain vascular endothelial cells

Nanomedicine. 2019 Feb:16:185-194. doi: 10.1016/j.nano.2018.11.016. Epub 2018 Dec 21.

Abstract

Diblock PLA-PEG nanoparticles were produced to establish the role of PEG chain length on brain vascular endothelial cell transcytosis. 100-nm nanoparticles tagged with fluorescent pyrene butanol and coated with PEG chains (Mw: 1-10 kDa), at similar PEG surface density, were used to study endocytosis and transcytosis phenomena on mouse vascular endothelial cell monolayers. The transport mechanisms were then investigated through inhibitory processes. Our results show that there is an evident correlation between PEG chain length and nanoparticle translocation. The highest transcytosis rates were obtained with PEG5000 and PEG10000 and macropinocytosis appeared to play a central role in cell uptake. This study constitutes the first systematic exploration of the role of PEG chain length on nanoparticle endocytosis and transcytosis in an in vitro model of the blood-brain barrier.

Keywords: Colloidal stability; Endocytosis; Mechanisms; PEG length; PLA-PEG nanoparticles; Transcytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology*
  • Cell Line
  • Cell Survival / drug effects
  • Endocytosis / drug effects
  • Endothelial Cells / metabolism*
  • Mice
  • Nanoparticles / adverse effects
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry*
  • Transcytosis / physiology*

Substances

  • monomethoxypolyethyleneglycol-polylactide block copolymer
  • Polyethylene Glycols