This “sweet spot” occurs in nanoparticles 30 to 50 nmin diameter where ligand density is optimal.
Unfortunately, studies elucidating the effect of nanoparticle diameter on uptake were conducted
primarily on immortalized cell lines. Because each cell type possesses a unique phenotype, optimal
nanoparticle uptake size may depend on the cell being assayed (e.g., immortalized HeLa versus
primary macrophage cells). Each cell type can express varying levels of target receptor and can
utilize different internalization pathways. Thus, it will be necessary to expand nanoparticle studies
to include both immortalized and primary cells in different cell culture configurations (monolayer
versus three dimensional). Only then will we be able to identify broad-scope design parameters
for optimal uptake and accumulation in cells