Interaction of densely polymer-coated gold nanoparticles with epithelial Caco-2 monolayers.

We synthesized a library of polymer-coated gold nanoparticles (AuNPs) with well-defined sizes (5, 10, and 20 nm) and surface properties, and investigated their efficiency to cross the Caco-2 epithelial barrier and disrupt tight junctions connecting the cellular barrier. The positively charged and hydrophobic polymer-coated AuNPs showed little or no translocation across the model Caco-2 monolayer. Most of these positive and hydrophobic nanoparticles were either bound to the surface or internalized within the cell. The neutral and negatively charged polymer-coated AuNPs with a size of 5 nm showed a significantly higher translocation. All polymer-coated AuNPs induced the translocation of small molecules across the cellular monolayer, suggesting the loosening of the paracellular tight junction joining individual cells. The decrease in the TEER values of the monolayers supported the opening of the tight junctions. These tight junctions fully recovered for most polymer-coated AuNPs 12 h after removal of the nanoparticles. The exception was the cationic polymer-coated AuNPs in which the barrier function only recovered up to 62%. The library of polymer-coated AuNPs showed no apparent signs of hemolysis to erythrocytes at physiological pH. Our investigation has provided insight on the influence of polymer coatings on the epithelial barrier.