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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

Mohammad Ahmad Al-Natour

Ali Alazzo

Dong-Hyun Kim

Cameron Alexander



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.

Journal Article Type Article
Publication Date Nov 12, 2019
Journal International Journal of Pharmaceutics: X
Electronic ISSN 2590-1567
Publisher Elsevier
Peer Reviewed Peer Reviewed
Article Number 100036
APA6 Citation Al-Natour, M. A., Alazzo, A., Ghaemmaghami, A. M., Kim, D., & Alexander, C. (2019). LC-MS metabolomics comparisons of cancer cell and macrophage responses to methotrexate and polymer- encapsulated methotrexate. International Journal of Pharmaceutics: X, https://doi.org/10.1016/j.ijpx.2019.100036
DOI https://doi.org/10.1016/j.ijpx.2019.100036
Publisher URL https://www.sciencedirect.com/science/article/pii/S2590156719300507

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