Mass spectrometry based techniques for in vivo quantification of fate and effects of engineered nanoparticles

Abstract

Engineered nanoparticles especially the gold nanoparticles (AuNPs) are widely used in various biomedical applications such as drug delivery, cancer treatment, biomedical imaging, diagnosis etc. To a large extent, their reported low toxicity to mammals seems to be one of the important features that make them to be desired in such applications. Most toxicological, uptake and biodistribution studies of engineered nanoparticles are often performed using in vitro systems however since the behavior of such materials are quite different in in vivo systems, studies focusing on the fate and effects of engineered nanoparticles in vivo are imperative. Also, biodistribution of engineered nanoparticles in biological systems are often performed by determining the levels of nanoparticles core only but since most engineered nanoparticles are often surface- functionalized as in AuNPs, techniques that allow for the determination of levels in both the nanoparticle core and the monolayer capping of the nanoparticle are more promising to provide concise information on the fate and effects of nanoparticles in biological systems. In the proposed research, mass spectrometric based imaging techniques; laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and laser desorption/ionization mass spectrometry (LDI-MS) would be used to quantify the fate and effects of AuNPs in vivo in mice. The LA-ICP-MS would be used to monitor the distributions of the nanoparticle core material while the LDI-MS imaging would be used to track the distribution on the surface monolayers of the nanoparticles. These techniques have the potential to track biodistribution at the organ and suborgan levels, providing information on the exact localization of nanoparticles within a particular organ, e.g. white versus red pulp of the spleen, kuppfer cells versus hepatocytes of the liver, glomeruli versus blood vessels in the kidney etc., as such, the correlation between the fate and the effects of AuNPs can be better understood. It is also anticipated that the data from this study could result in the identification of potential biomarkers of exposure to AuNPs in vivo.