Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway.
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.
Lai
Samuel K
SK
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, USA.
Hida
Kaoru
K
Man
Stan T
ST
Chen
Clive
C
Machamer
Carolyn
C
Schroer
Trina A
TA
Hanes
Justin
J
D001692:Biological Transport; D021941:Caveolae / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002966:Clathrin / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism* / Q000648:ultrastructure; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors
D002966:Clathrin; D011108:Polymers