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 language | English (US) |
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Pages (from-to) | 2876-2884 |
Number of pages | 9 |
Journal | Biomaterials |
Volume | 28 |
Issue number | 18 |
DOIs | |
State | Published - 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