Developing a Drug Screening Platform: MALDI-Mass Spectrometry Imaging of Paper-Based Cultures

Many potential chemotherapeutics fail to reach patients. One of the key reasons is that compounds are tested during the drug discovery stage in two-dimensional (2D) cell cultures, which are often unable to accurately model in vivo outcomes. Three-dimensional (3D) in vitro tumor models are more predi...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2019-12, Vol.91 (24), p.15370-15376
Main Authors: Tobias, Fernando, McIntosh, Julie C, LaBonia, Gabriel J, Boyce, Matthew W, Lockett, Matthew R, Hummon, Amanda B
Format: Article
Language:English
Subjects:
Analytical chemistry
Antineoplastic Agents - pharmacology
Cell culture
Cell Culture Techniques - instrumentation
Chemistry
Coupling (molecular)
Drug Evaluation, Preclinical - instrumentation
Drug Evaluation, Preclinical - methods
Drug screening
drug therapy
drugs
HCT116 Cells
Humans
image analysis
Ionization
Ions
Mass spectrometry
Mass spectroscopy
matrix-assisted laser desorption-ionization mass spectrometry
neoplasms
Scientific imaging
Screening
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Spectroscopy
Three dimensional models
Two dimensional models
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Summary:Many potential chemotherapeutics fail to reach patients. One of the key reasons is that compounds are tested during the drug discovery stage in two-dimensional (2D) cell cultures, which are often unable to accurately model in vivo outcomes. Three-dimensional (3D) in vitro tumor models are more predictive of chemotherapeutic effectiveness than 2D cultures, and thus, their implementation during the drug screening stage has the potential to more accurately evaluate compounds earlier, saving both time and money. Paper-based cultures (PBCs) are an emerging 3D culture platform in which cells suspended in Matrigel are seeded into paper scaffolds and cultured to generate a tissue-like environment. In this study, we demonstrate the potential of matrix-assisted laser desorption/ionization–mass spectrometry imaging with PBCs (MALDI-MSI-PBC) as a drug screening platform. This method discriminated regions of the PBCs with and without cells and/or drugs, indicating that coupling PBCs with MALDI-MSI has the potential to develop rapid, large-scale, and parallel mass spectrometric drug screens.
ISSN:0003-2700
1520-6882
1520-6882
DOI:10.1021/acs.analchem.9b03536