Dataset Information

Analysis of Chemotherapeutic Drug Delivery at the Single Cell Level Using 3D-MSI-TOF-SIMS.

ABSTRACT: In this work, we show the advantages of label-free, tridimensional mass spectrometry imaging using dual beam analysis (25 keV Bi3+) and depth profiling (20 keV with a distribution centered at Ar1500+) coupled to time of flight secondary ion mass spectrometry (3D-MSI-TOF-SIMS) for the study of A-172 human glioblastoma cell line treated with B-cell lymphoma 2 (Bcl-2) inhibitor ABT-737. The high spatial (~250 nm) and high mass resolution (m/?m ~10,000) of TOF-SIMS permitted the localization and identification of the intact, unlabeled drug molecular ion (m/z 811.26 C42H44ClN6O5S2- [M - H]-) as well as characteristic fragment ions. We propose a novel approach based on the inspection of the drug secondary ion yield, which showed a good correlation with the drug concentration during cell treatment at therapeutic dosages (0-200 ?M with 4 h incubation). Chemical maps using endogenous molecular markers showed that the ABT-737 is mainly localized in subsurface regions and absent in the nucleus. A semiquantitative workflow is proposed to account for the biological cell diversity based on the spatial distribution of endogenous molecular markers (e.g., nuclei and cytoplasm) and secondary ion confirmation based on the ratio of drug-specific fragments to molecular ion as a function of the therapeutic dosage. Graphical Abstract ?.

SUBMITTER: Vanbellingen QP

PROVIDER: S-EPMC5088064 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of Chemotherapeutic Drug Delivery at the Single Cell Level Using 3D-MSI-TOF-SIMS.

Vanbellingen Quentin P QP Castellanos Anthony A Rodriguez-Silva Monica M Paudel Iru I Chambers Jeremy W JW Fernandez-Lima Francisco A FA

Journal of the American Society for Mass Spectrometry 20160831 12

In this work, we show the advantages of label-free, tridimensional mass spectrometry imaging using dual beam analysis (25 keV Bi3+) and depth profiling (20 keV with a distribution centered at Ar1500+) coupled to time of flight secondary ion mass spectrometry (3D-MSI-TOF-SIMS) for the study of A-172 human glioblastoma cell line treated with B-cell lymphoma 2 (Bcl-2) inhibitor ABT-737. The high spatial (~250 nm) and high mass resolution (m/Δm ~10,000) of ...[more]

PMID: 27582118

Similar Datasets

Project description:Combinatorial approaches to materials discovery offer promising potential for the rapid development of novel polymer systems. Polymer microarrays enable the high-throughput comparison of material physical and chemical properties-such as surface chemistry and properties like cell attachment or protein adsorption-in order to identify correlations that can progress materials development. A challenge for this approach is to accurately discriminate between highly similar polymer chemistries or identify heterogeneities within individual polymer spots. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) offers unique potential in this regard, capable of describing the chemistry associated with the outermost layer of a sample with high spatial resolution and chemical sensitivity. However, this comes at the cost of generating large scale, complex hyperspectral imaging data sets. We have demonstrated previously that machine learning is a powerful tool for interpreting ToF-SIMS images, describing a method for color-tagging the output of a self-organizing map (SOM). This reduces the entire hyperspectral data set to a single reconstructed color similarity map, in which the spectral similarity between pixels is represented by color similarity in the map. Here, we apply the same methodology to a ToF-SIMS image of a printed polymer microarray for the first time. We report complete, single-pixel molecular discrimination of the 70 unique homopolymer spots on the array while also identifying intraspot heterogeneities thought to be related to intermixing of the polymer and the pHEMA coating. In this way, we show that the SOM can identify layers of similarity and clusters in the data, both with respect to polymer backbone structures and their individual side groups. Finally, we relate the output of the SOM analysis with fluorescence data from polymer-protein adsorption studies, highlighting how polymer performance can be visualized within the context of the global topology of the data set.

Dataset Information

Analysis of Chemotherapeutic Drug Delivery at the Single Cell Level Using 3D-MSI-TOF-SIMS.

Publications

Analysis of Chemotherapeutic Drug Delivery at the Single Cell Level Using 3D-MSI-TOF-SIMS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets