Impact of agglomeration state of gold particles on pulmonary toxicity

Impact of agglomeration state of gold particles on pulmonary toxicity Nanoparticle (NP) toxicity testing comes with many challenges. One of them is agglomeration/aggregation of nanoparticles in physiological media. In this study, we address the effect of agglomerated versus single particle suspensions of nanosized and submicronsized gold on the inflammatory response in the lung. Single nanoparticles may pose a greater hazard to the human body compared to nanoparticles in larger aggregates or micronsized particles, possibly due to their ability to cross barriers and by-pass the pulmonary immune system. Colloidal gold was chosen as a model particle to study effects on lung inflammatory markers in broncho alveolar lavage fluid (BALF) after intratracheal instillation in the rat. A single dose of 1 mg of spherical gold particles (stock suspensions in citrate buffer) of 50 nanometer (nm) or 250 nm is diluted either by ultrapure water or by adding phosphate buffered saline (PBS). Particles diluted in ultrapure water are well dispersed, while the citrate coating is disturbed and agglomerates are formed when diluting in PBS. A single dose of 1 mg DQ12 quartz is used as a positive control for pulmonary inflammation. Extensive characterization of the particle suspensions has been performed. Cell differential count, cell damage and inflammation were determined in BALF after 3 and 24 hours post exposure. The primary particle size, the gold concentration in the suspensions and particle purity are important features to verify, since they may deviate from the manufacturer’s description. The 250 nm particles were smaller in size and build up from multiple smaller units, the concentration of gold was less than described and some silicium residues were found in the suspension. There are no major differences in how the lung deals with agglomerated versus single citrate stabilized gold particles of different sizes after intratracheal instillation. Our results indicate that a suspension of single 50 nm and 250 nm gold nanoparticles as well as agglomerated 50 nm and 250 nm gold nanoparticles resulted in a very mild inflammatory response. We conclude that single nanosized gold particles do not possess a greater hazard when using pulmonary inflammation as a marker for toxicity than agglomerated gold nanoparticles. Trefwoorden /