Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway

Samuel K. Lai, Kaoru Hida, Stan T. Man, Clive Chen, Carolyn Machamer, Trina A. Schroer, Justin Hanes

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2876-2884
Number of pages9
JournalBiomaterials
Volume28
Issue number18
DOIs
StatePublished - Mar 30 2007

Keywords

  • Gene delivery
  • Intracellular delivery
  • Non-caveolae
  • Non-clathrin
  • Size
  • Trafficking

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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