High-efficiency mechanically assisted alkaline extraction of nanoparticles from biological tissues for spICP-MS analysis.

The widespread use and increased exposure of nanoparticles call for technology to quantify their concentration and size distribution in biological matrices. As ex situ evaluation, facile extraction with high fidelity and efficiency is critical. In this work, single particle inductively coupled plasma mass spectrometry (spICP-MS) was used for nanoparticle number and distribution analysis, where a facile and highly efficient mechanically assisted alkaline digestion has been developed to extract nanoparticles at low alkali concentration. The optimization was performed using chicken tissues in vitro mixed with 30 nm gold nanoparticles, mixture of 30 nm and 60 nm gold nanoparticles, and 45 nm silver nanoparticles, respectively, which is, then, mechanically ground to form tissue homogenate and 2% TMAH is added. The nanoparticles are extracted with a recovery of more than 94% for all the spiked nanoparticle tissue samples. The extraction method has also been attempted to be applied to extract single-sized gold nanoparticles from various organs of mice mixed in vivo with the nanoparticles through intravenous injection, and led to consistent results with acid digestion. Mice injected intravenously with double-sized gold nanoparticle mixture were also studied, further showing that gold nanoparticles of 30 nm and 60 nm have no significant difference in their biodistribution in the same organ. To the best of our knowledge, this is the first attempt for multiple nanoparticles being extracted simultaneously and measured quantitatively from various organs, such as the heart, liver, spleen, lungs, and kidneys. We believe this method is beneficial to the safety assessment and toxicokinetics studies for nanoparticles in tissues.