Mohammad Ahmad Al-Natour
LC-MS metabolomics comparisons of cancer cell and macrophage responses to methotrexate and polymer-encapsulated methotrexate
Al-Natour, Mohammad Ahmad; Alazzo, Ali; Ghaemmaghami, Amir M; Kim, Dong-Hyun; Alexander, Cameron
Authors
Ali Alazzo
Professor AMIR GHAEMMAGHAMI AMIR.GHAEMMAGHAMI@NOTTINGHAM.AC.UK
Professor of Immunology and Immuno- Bioengineering
DONG-HYUN KIM Dong-hyun.Kim@nottingham.ac.uk
Associate Professor
Professor CAMERON ALEXANDER CAMERON.ALEXANDER@NOTTINGHAM.AC.UK
Professor of Polymer Therapeutics
Abstract
Methotrexate (MTX) is a folate analogue antimetabolite widely used for the treatment of rheumatoid arthritis and cancer. A number of studies have shown that MTX delivered via nanoparticle carriers is more potent against cancer cells than free MTX, a phenomenon attributed to higher cellular uptake of the particles compared to the saturable folate receptor pathway. In this study, a cell-based global metabolic profiling approach was applied to study the effects of MTX in both free drug form and when encapsulated in-poly(lactide-co-glycolide) (PLGA) nanoparticles on a cancer cell line, A549, and also on human-like THP-1 macrophages. The results showed that MTX loaded nanoparticles had less impact on the macrophages than free MTX, and the effects on macrophages were limited to changes in nucleotide metabolism and suppression of the tricarboxylic acid cycle, whereas free MTX also led to a drop in glycolytic activity and impairment in redox homeostasis. In contrast, MTX loaded nanoparticles showed a greater impact on A549 cells than the free drug, which was in accord with studies in other cell lines in prior literature with MTX-carrier nanoparticles.
Citation
Al-Natour, M. A., Alazzo, A., Ghaemmaghami, A. M., Kim, D.-H., & Alexander, C. (2019). LC-MS metabolomics comparisons of cancer cell and macrophage responses to methotrexate and polymer-encapsulated methotrexate. International Journal of Pharmaceutics: X, 1, Article 100036. https://doi.org/10.1016/j.ijpx.2019.100036
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 27, 2019 |
Online Publication Date | Nov 12, 2019 |
Publication Date | 2019-12 |
Deposit Date | Oct 3, 2019 |
Publicly Available Date | Oct 3, 2019 |
Journal | International Journal of Pharmaceutics: X |
Electronic ISSN | 2590-1567 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 1 |
Article Number | 100036 |
DOI | https://doi.org/10.1016/j.ijpx.2019.100036 |
Keywords | Pharmaceutical Science |
Public URL | https://nottingham-repository.worktribe.com/output/2741856 |
Publisher URL | https://www.sciencedirect.com/science/article/pii/S2590156719300507 |
Contract Date | Oct 3, 2019 |
Files
LC-MS metabolomics comparisons of cancer cell and macrophage responses to methotrexate and polymer-encapsulated methotrexate
(1.3 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
You might also like
Investigating NF-kappa B signaling in lung fibroblasts in 2D and 3D culture systems
(2015)
Journal Article
Allergen recognition by innate immune cells: critical role of dendritic and epithelial cells
(2013)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search