Privileged Delivery of Polymer Nanoparticles to the Perinuclear Region of Live Cells via a Non-Clathrin, Non-Degradative Pathway

Biomaterials. 2007 Jun;28(18):2876-84. doi: 10.1016/j.biomaterials.2007.02.021. Epub 2007 Feb 27.

Abstract

The efficacy of many therapeutic molecules could be greatly enhanced by polymer-based nanoparticle systems capable of delivering them to the direct vicinity of the cell nucleus. However, degradation of the particles and encapsulated drugs within the enzyme-rich and low-pH environments of the endo/lysosomal pathway of cells has dramatically limited the efficacy of such systems. In this paper, we discovered that small polymeric particles (<25 nm) but not larger particles (>42 nm) enter live cells via a novel mechanism that leads to trafficking outside the endo/lysosomal pathway. Sub-25 nm particles rapidly transport to the perinuclear region of cells in vesicles that never acidify. The pathway is non-degradative, cholesterol independent, and non-clathrin and non-caveolae mediated. This privileged non-acidic pathway may be general since our results are surprisingly obtained with standard latex polymer beads without addition of ligands and may, therefore, provide a promising route for drug and gene delivery using biomaterial-based nanodevices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Caveolae / metabolism*
  • Cell Nucleus / metabolism*
  • Cell Nucleus / ultrastructure
  • Clathrin / metabolism
  • Cytoplasm / metabolism*
  • Cytoplasm / ultrastructure
  • Drug Delivery Systems
  • HeLa Cells
  • Humans
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Nanotechnology / methods
  • Polymers / administration & dosage
  • Polymers / chemistry
  • Polymers / pharmacokinetics*
  • Time Factors

Substances

  • Clathrin
  • Polymers