Surface Charge Controls the Suborgan Biodistributions of Gold Nanoparticles

Surface chemistry plays a deciding role in nanoparticle biodistribution, yet very little is known about how surface chemistry influences the suborgan distributions of nanomaterials. Here, using quantitative imaging based on laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), we demonstrate that surface charge dictates the suborgan distributions of nanoparticles in the kidney, liver, and spleen of mice intravenously injected with functionalized gold nanoparticles. Images of the kidney show that positively charged nanoparticles accumulate extensively in the glomeruli, the initial stage in filtering for the nephron, suggesting that these nanoparticles may be filtered by the kidney at a different rate than the neutral or negatively charged nanoparticles. We find that positively and negatively charged nanoparticles accumulate extensively in the red pulp of the spleen. In contrast, uncharged nanoparticles accumulate in the white pulp and marginal zone of the spleen to a greater extent than the positively or negatively charged nanoparticles. Moreover, these uncharged nanoparticles are also more likely to be found associated with Kupffer cells in the liver. Positively charged nanoparticles accumulate extensively in liver hepatocytes, whereas negatively charged nanoparticles show a broader distribution in the liver. Together these observations suggest that neutral nanoparticles having 2 nm cores may interact with the immune system to a greater extent than charged nanoparticles, highlighting the value of determining the suborgan distributions of nanomaterials for delivery and imaging applications.