Gold nanoparticles translocate from the lung into the blood in man and accumulate at sites of vascular inflammation in apolipoproteinE knockout mice

Abstract

Engineered nanoparticles have similar properties to particulate air pollution and inhalation exposure may cause adverse effects on the cardiovascular system. 14 healthy male volunteers were exposed to gold nanoparticles (diameter 21 nm, mass concentration 117μg/m 3 ) for 2 hours during intermittent exercise. Blood was collected before and after the exposure, and urine was collected for 24 hours. Samples were analysed for gold particles using high-resolution inductively-coupled mass spectrometry. In a parallel study apolipoproteinE knockout mice were fed a high fat diet for 10 weeks. Five nanometer gold nanoparticles, or saline, were administered to the lung for the last 5 weeks of feeding. Following inhalation of gold nanoparticles, gold was detected in the bloodstream in nearly all the subjects. The time course was consistent with an active process with accumulation over 24 hours. Gold was detected in all urine samples with a mean concentration of 35 ± 23 ng/mL. Gold was detected in the blood and liver of gold-, but not saline-, instilled mice. Gold concentrations within the atherosclerotic blood vessels (aortic arch; 793±384 ng gold/g tissue) were higher (P=0.01; n=6-8) than non-atherosclerotic vessels (35±16 ng/mL) of gold-instilled mice. Raman spectroscopy confirmed the presence of gold particulate in atherosclerotic plaques. Gold nanoparticles translocate into the bloodstream following inhalation exposure in man and accumulate at sites of vascular inflammation in man. This translocation of particles and accumulation in atherosclerotic plaque may be one of the mechanisms by which inhaled particulate mediates its adverse effects.