TY - JOUR
T1 - Developing a Drug Screening Platform
T2 - MALDI-Mass Spectrometry Imaging of Paper-Based Cultures
AU - Tobias, Fernando
AU - McIntosh, Julie C.
AU - Labonia, Gabriel J.
AU - Boyce, Matthew W.
AU - Lockett, Matthew R.
AU - Hummon, Amanda B.
N1 - Funding Information:
G.J.L. and A.B.H. were supported by the National Institutes of Health (R01GM110406). A.B.H. was also supported by the National Science Foundation (CAREER Award, CHE-1351595). J.C.M. and M.R.L. were supported by the National Institutes of Health (R35GM128697). The 15 T Bruker SolariX FTICR instrument was supported by NIH Award Number Grant S10 OD018507. F.T. was supported by Ohio State Start-Up funds to A.B.H. M.W.B. would like to thank the Graduate School of UNC for support with a Dissertation Completion Fellowship. The authors would like to thank Dr. Arpad Somogyi with the initial FTICR optimizations and Mr. Tyler Larson for his helpful insights.
Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/12/17
Y1 - 2019/12/17
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.analchem.9b03536
DO - 10.1021/acs.analchem.9b03536
M3 - Article
C2 - 31755703
AN - SCOPUS:85076734145
SN - 0003-2700
VL - 91
SP - 15370
EP - 15376
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 24
ER -