Several studies have shown that Caco-2 cells have the capability to transport peptides and proteins from their apical to basal surfaces when these molecules are linked to vitamin B 1 2 (VB 1 2 ). In this study we have extended these studies and have shown that Caco-2 cells are also able to internalize and transport VB 1 2 -modifed nanoparticles from their apical to basal surfaces. Uptake and transport of nanoparticles was found to occur in both a VB 1 2 -dependent intrinsic factor (IF)-independent manner as well as in a VB 1 2 -dependent IF-dependent manner. Both IF-independent and IF-dependent VB 1 2 -mediated uptake and transport were dependent upon the surface density of VB 1 2 as a reduction in surface modification of the nanoparticles with VB 1 2 resulted in a reduced level of both VB 1 2 -mediated and IF-mediated uptake. At lower levels of VB 1 2 modification there was no apparent non-IF-mediated uptake; however, VB 1 2 -IF-mediated uptake was still measurable. These studies show that Caco-2 cell cultures are a suitable model for the study of VB 1 2 -mediated uptake and transport of nanoparticles, and suggest that for effective oral uptake of VB 1 2 -coated nanoparticles high surface densities of VB 1 2 are required.