Method to Investigate the Distribution of Water-Soluble Drug-Delivery Systems in Fresh Frozen Tissues Using Imaging Mass Cytometry

Abstract

Imaging mass cytometry (IMC) offers the opportunity to image metal- and heavy halogen-containing xenobiotics in a highly multiplexed experiment with other immunochemistry-based reagents to distinguish uptake into different tissue structures or cell types. However, in practice, many xenobiotics are not amenable to this analysis, as any compound which is not bound to the tissue matrix will delocalize during aqueous sample-processing steps required for IMC analysis. Here, we present a strategy to perform IMC experiments on a water-soluble polysarcosine-modified dendrimer drug-delivery system (S-Dends). This strategy involves two consecutive imaging acquisitions on the same tissue section using the same instrumental platform, an initial laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MSI) experiment followed by tissue staining and a standard IMC experiment. We demonstrated that settings can be found for the initial ablation step that leave sufficient residual tissue for subsequent antibody staining and visualization. This workflow results in lateral resolution for the S-Dends of 2 μm followed by imaging of metal-tagged antibodies at 1 μm.

Tellurophene‐Tagging of Teniposide Facilitates Monitoring by Mass Cytometry

“…Recently, Strittmatter and co-workers presented a new method that minimizes diffusion of target-bound MCactive small molecules for visualization by IMC. [28] The scope of this work was limited to a water-soluble polysarcosine-modified dendrimer drug-delivery system (DDS) carrying three isotopically pure lanthanides ( 141 Pr, 159 Tb, and 165 Ho), but suggests similar approaches may be fruitful. Substantial increases in signal could also be realized through synthesis of the isotopically enriched Te-teniposide ( 125 Te is only 7 % of natural Te abundance), which in theory could lead to an over 10-fold increase in signal.…”

ICP-MS-Based Methodology In Metallomics: Towards Single Particle Analysis, Single Cell Analysis, And Spatial Metallomics

“…The distributions of metals and proteins in the same tissue section were obtained using a strategy of two consecutive imaging acquisitions with LA-ICP-MS analysis followed by tissue staining and a standard IMC analysis (Fig 1). 100 The LA-ICP-MS technique may be further expanded to image mRNAs or DNAs once suitable metal probes are developed, realizing spatial multi-omics analysis using the same LA-ICP-MS instrument.…”

Highway to Success—Developing Advanced Polymer Therapeutics

“…Figure 3 shows the granular distribution of a lanthanide labeled polysarcosine star polymer (S-Dend 159Tb), with molecular weight 115 kDa, in mouse duodenum tissue following intravenous dosing. [151] Integrated molecular imaging and advanced image analysis have the opportunity to make a huge impact in the clinical translation of polymer therapeutics.…”

“…This is a very different safety assessment to a typical small molecule. A "safe by design" approach to nanomedicines has been proposed for inorganic particles however many of the [151] Copyright 2021, American Chemical Society.…”

“…White arrow indicates large blood vessel. Adapted with permission [151]. Copyright 2021, American Chemical Society.…”