Quantifying the Sub‐Cellular Distributions of Gold Nanospheres Taken Up by Cells through Stepwise, Site‐Selective Etching

A quantitative understanding of the sub-cellular distributions of nanospheres taken up by cells is of key importance to the development of effective nanomedicine. With gold nanospheres as a model system, here we demonstrate, for the first time, how to quantify the numbers of nanospheres bound to plasma membrane, accumulated in cytosol, and entrapped in endo-lysosomes, respectively, through stepwise, site-selective etching. Our results indicate that the chance for nanospheres to escape from endo-lysosomes is insensitive to the presence of targeting ligand although ligand-receptor binding has been documented as a critical factor in triggering internalization. Furthermore, the presence of serum proteins is shown to facilitate the binding of nanospheres to plasma membrane lacking the specific receptor. Collectively, these findings confirm the potential of stepwise etching in quantitatively analyzing the sub-cellular distributions of nanospheres taken up by cells in an effort to optimize the therapeutic effect.