Dual Mass Spectrometric Tissue Imaging of Nanocarrier Distributions and Their Biochemical Effects

Abstract

Nanomaterial-based drug delivery vehicles are able to deliver therapeutics in a controlled, targeted manner. Currently, however, there are limited analytical methods that can detect both nanomaterial distributions and their biochemical effects concurrently. In this study, we demonstrate that matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) can be used together to obtain nanomaterial distributions and biochemical consequences. These studies employ nanoparticle-stabilized capsules (NPSCs) loaded with siRNA as a testbed. MALDI-MSI experiments on spleen tissues from intravenously injected mice indicate that NPSCs loaded with TNF-a-specific siRNA cause changes to lipid composition in white pulp regions of the spleen, as anticipated, based on pathways known to be affected by TNF-a, whereas NPSCs loaded with scrambled siRNA do not cause the predicted changes. Interestingly, FA-ICP-MSI experiments reveal that the NPSCs primarily localize in the red pulp, suggesting that the observed changes in lipid composition are due to diffusive rather than localized effects on TNF-α production. Such information is only accessible by combining data from the two modalities, which we accomplish by using the heme signals from MAFDI-MSI and Fe signals from FA-ICP-MSI to overlay the images. Several unexpected changes in lipid composition also occur in regions where the NPSCs are found, suggesting that the NPSCs themselves can influence tissue biochemistry as well.

Emerging Computational Methods in Mass Spectrometry Imaging

“…[8,19,20] Different MSI modalities have been combined to obtain complementary molecular and spatial information for the same sample. [212][213][214][215][216][217][218][219][220][221][222][223][224] For example, SIMS and MALDI have been used to obtain correlative imaging data of cholesterol and other small molecules with proteins. [212] Meanwhile, DESI and MALDI have been used in sequence on the same tissue section to obtain spatial maps of lipids and proteins.…”

Delivery of drugs, proteins, and nucleic acids using inorganic nanoparticles

“…Although some uncertainty in regards to the biological fate of the gold nanomaterials is to be considered, there are ways to overcome this limitation by controlling the surface properties such as surface charge [66] which will be critical to the future advancement of gold-based delivery platforms. [143,188].…”

Mass Spectrometric Biosensing: A Powerful Approach for Multiplexed Analysis of Clinical Biomolecules

“…The extension of the LDI-MS method was later reported for the rapid quantification of cell surface-bound and internalized NPs, with which how cell-surface proteoglycans influence NP binding and cell uptakewere demonstrated . Applications of this method also include monitoring the association and dissociation of NP-based host–guest interactions in cells and revealing divergences of NP stability and biochemical effects in different organs and suborgans. , Because NP surface-ligand m / z are used as the readout, the established LDI-MS biosensing platform minimizes the biosample amount for imaging analysis, making it a potential tool for clinical applications of biopsies and microbiopsies.…”

“…135 Applications of this method also include monitoring the association and dissociation of NP-based host−guest interactions in cells 136 and revealing divergences of NP stability and biochemical effects in different organs and suborgans. 137,138 Because NP surface-ligand m/z are used as the readout, the established LDI-MS biosensing platform minimizes the biosample amount for imaging analysis, making it a potential tool for clinical applications of biopsies and microbiopsies. However, some researchers consider that the preceding label-based approaches carry the risk of tag detachment over time.…”