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

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.

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.

PMID: 17363053 [PubMed - indexed for MEDLINE]