Surface Chemistry of Gold Nanoparticles Mediates Their Exocytosis in Macrophages

Significant quantities of synthetic nanoparticles circulating in the body are cleared and retained for long periods of time in the resident macrophages of the mononuclear phagocytic system (MPS), increasing the likelihood of nanoparticle-mediated chronic toxicity. To date, there has been limited effort to understand how these nanoparticles leave the macrophages. Here, we demonstrate that the native surface chemistries of gold nanoparticles (GNPs) and their subsequent opsonization by serum proteins play critical roles in the exocytosis patterns in macrophages. The cationic GNPs were retained in the cells for a relatively long time, likely due to their intracellular agglomeration. In contrast, the PEGylated GNPs migrated in the cytoplasm in the form of individual particles and exited the cells rapidly because the PEG coating mitigated interactions between GNPs and intracellular proteins. Additionally, their exocytosis pattern was not significantly governed by the size, particularly in the range from 10 to 40 nm. These results suggest that systemic excretion and toxicity of nanoparticles cleared in the MPS could be modulated by engineering their surface chemistry.