Dual-Mode Mass Spectrometric Imaging for Determination of in Vivo Stability of Nanoparticle Monolayers

Effective correlation of the in vitro and in vivo stability of nanoparticle-based platforms is a key challenge in their translation into the clinic. Here, we describe a dual imaging method that site-specifically reports the stability of monolayer-functionalized nanoparticles in vivo. This approach uses laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging to monitor the distributions of the nanoparticle core material and laser desorption/ionization mass spectrometry (LDI-MS) imaging to report on the monolayers on the nanoparticles. Quantitative comparison of the images reveals nanoparticle stability at the organ and suborgan level. The stability of particles observed in the spleen was location-dependent and qualitatively similar to in vitro studies. In contrast, in vivo stability of the nanoparticles in the liver differed dramatically from in vitro studies, demonstrating the importance of in vivo assessment of nanoparticle stability.