Absolute Quantification of Nanoparticle Interactions with Individual Human B Cells by Single Cell Mass Spectrometry

Abstract

We report on the absolute quantification of nanoparticle interactions with individual human B cells using quadrupolebased inductively coupled plasma mass spectrometry (ICP-MS). This method enables the quantification of nanoparticle−cell interactions at single nanoparticle and single cell levels. We demonstrate the efficient and accurate detection of individually suspended B cells and found an ∼100-fold higher association of colloidally stable positively charged nanoparticles with single B cells than neutrally charged nanoparticles. We confirmed that these nanoparticles were internalized by individual B cells and determined that the internalization occurred via energy-dependent pathways consistent with endocytosis. Using dual analyte ICP-MS, we determined that >80% of single B cells were positive for nanoparticles. Our study demonstrates an ICP-MS workflow for the absolute quantification of nanoparticle−cell interactions with single cell and single nanoparticle resolution. This unique workflow could inform the rational design of various nanomaterials for controlling cellular interactions, including immune cell−nanoparticle interactions.

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Quantifying Intracellular Nanoparticle Distributions with Three-Dimensional Super-Resolution Microscopy

“…SP-ICP-MS allows us to quantify the mass of individual AuNPs at single-particle resolutions to estimate their approximate sizes. The SP-ICP-MS method then allows us to determine the corresponding colloidal stability of the AuNPs as aggregates would be registered as single AuNPs of significantly larger masses (i.e., sizes) than colloidally stable AuNPs. ,− Figure S15 demonstrates that there is no significant difference ( p > 0.9999) in the mean values of the distributions of HEP- or PEG-AuNPs, respectively, in any of the tested conditions compared to the ultrapure H 2 O control group. These results suggest that the AuNPs may not significantly aggregate intracellularly.…”

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