Quantitative imaging of the sub-organ distributions of nanomaterials in biological tissues via laser ablation inductively coupled plasma mass spectrometry.

Abstract

Nanomaterials have been employed in many biomedical applications, and their distributions in biological systems can provide an understanding of their behavior in vivo. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) can be used to determine the distributions of metal-based NMs in biological systems. However, LA-ICP-MS has not commonly been used to quantitatively measure the cell-specific or sub-organ distributions of nanomaterials in tissues. Here, we describe a new platform that uses spiked gelatin standards with control tissues on top to obtain an almost perfect tissue mimic for quantitative imaging purposes. In our approach, gelatin is spiked with both nanomaterial standards and an internal standard to improve quantitation and image quality. The value of the developed approach is illustrated by determining the sub-organ distributions of different metal-based and metal-tagged polymeric nanomaterials in mice organs. The LA-ICP-MS images reveal that the chemical and physical properties of the nanomaterials cause them to distribute in quantitatively different extents in spleens, kidneys, and tumors, providing new insight into the fate of nanomaterials in vivo. Furthermore, we demonstrate that this approach enables quantitative co-localization of nanomaterials and their cargo. We envision this method being a valuable tool in the development of nanomaterial drug delivery systems.