Magnetic forces enable controlled drug delivery by disrupting endothelial cell-cell junctions

Nat Commun. 2017 Jun 8:8:15594. doi: 10.1038/ncomms15594.

Abstract

The vascular endothelium presents a major transport barrier to drug delivery by only allowing selective extravasation of solutes and small molecules. Therefore, enhancing drug transport across the endothelial barrier has to rely on leaky vessels arising from disease states such as pathological angiogenesis and inflammatory response. Here we show that the permeability of vascular endothelium can be increased using an external magnetic field to temporarily disrupt endothelial adherens junctions through internalized iron oxide nanoparticles, activating the paracellular transport pathway and facilitating the local extravasation of circulating substances. This approach provides a physically controlled drug delivery method harnessing the biology of endothelial adherens junction and opens a new avenue for drug delivery in a broad range of biomedical research and therapeutic applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / metabolism
  • Adherens Junctions / radiation effects*
  • Animals
  • Capillary Permeability / radiation effects*
  • Cell Line
  • Drug Delivery Systems / methods*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / radiation effects*
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Magnetic Fields*
  • Mice
  • Mice, Nude