INTRACELLULAR LOCALIZATION AND KINETICS OF UPTAKE AND CLEARANCE OF GOLD NANOPARTICLES IN PRIMARY HEPATIC CELLS

Abstract

Gold nanoparticles (AuNPs) used for therapeutic applications preferentially accumulate in the liver following exposure. However, uptake and clearance by hepatic cells are not well understood. Time-dependent intracellular localization, uptake and clearance of 30 nm AuNPs were monitored in primary rat hepatocytes and liver sinusoidal endothelial cells (LSECs). Confocal Raman microscopy studies demonstrated the differences in the localization of AuNPs in hepatic cells over a 24 h period. The uptake of unmodified AuNPs over 24 h was 17% and 55% for hepatocytes and LSECs. The uptake of poly(ethylene glycol)-coated AuNPs was 3% and 1% over 24 h in hepatocytes and LSECs, respectively. Both cell types expelled approximately 60–70% of intracellular AuNPs within seven days. AuNP accumulation resulted in the disruption of the pericanalicular actin between adjoining hepatocytes. These trends suggest that AuNPs may affect actin organization, which could impair hepatic function long term.