Adsorption/internalization kinetics and subcellular distribution

Gold nanorods (AuNRs) have an increasing presence in biomedical research, but it remains unclear how aspect ratio (AR) influences their subcellular distribution. Here, we quantified the cellular adsorption and internalization kinetics and correlated them with the subcellular distribution of AuNRs. It is found that the distribution ratio between internalized and surface-adsorbed AuNRs decreases with increasing AR, with modest AR of 3.2 being most favorable for long-efficient delivery into cells. Long edge and blunt tip, critical to the adsorption and internalization, are simultaneously satisfied by this modest AR. Other ARs cause obvious barriers in the intermediate steps, contributing to uneven subcellular AuNR accumulation. Additionally, internalization shifts from spontaneous wrapping to clathrin-mediated ATP-dependent endocytosis with increasing AR. Inhibition of the endocytic pathways can reduce the distribution ratio, with the magnitude of effect depending on their importance to the internalization. These findings extend our knowledge of the subcellular distribution mechanisms of non-spherical nanoparticles.