Nanoparticle Transport in Epithelial Cells: Pathway Switching Through Bioconjugation

The understanding and control of nanoparticle transport into and through cellular compartments is central to biomedical applications of nanotechnology. Here, it is shown that the transport pathway of 50 nm polystyrene nanoparticles decorated with vitamin B-12 in epithelial cells is different compared to both soluble B-12 ligand and unmodified nanoparticles, and this is not attributable to B-12 recognition alone. Importantly, the study indicates that vitamin B-12-conjugated nanoparticles circumnavigate the lysosomal compartment, the destination of soluble vitamin B-12 ligand. Whereas cellular trafficking of soluble B-12 is confirmed to occur via the clathrin-mediated pathway, transport of B-12-conjugated nanoparticles appears to predominantly take place by a route that is perturbed by caveolae-specific inhibitors. This data suggests that, following its conjugation to nanoparticles, in addition to dramatically increasing the cellular uptake of nanoparticles, the normal cell trafficking of B-12 is switched to an alternative pathway, omitting the lysosomal stage: a result with important implications for oral delivery of nanoparticulate diagnostics and therapeutics.