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Metabolic Signatures of Surface-Modified Poly(lactic- co-glycolic acid) Nanoparticles in Differentiated THP-1 Cells Derived with Liquid Chromatography-Mass Spectrometry-based Metabolomics

Al-Natour, Mohammad A; Abdelrazig, Salah; Ghaemmaghami, Amir M.; Alexander, Cameron; Kim, Dong Hyun

Metabolic Signatures of Surface-Modified Poly(lactic- co-glycolic acid) Nanoparticles in Differentiated THP-1 Cells Derived with Liquid Chromatography-Mass Spectrometry-based Metabolomics Thumbnail


Authors

Mohammad A Al-Natour

Salah Abdelrazig



Abstract

Polymeric nanoparticles (NPs) are widely used in preclinical drug delivery investigations, and some formulations are now in the clinic. However, the detailed effects of many NPs at the subcellular level have not been fully investigated. In this study, we used differentiated THP-1 macrophage cells, as a model, to investigate the metabolic changes associated with the use of poly (lactic-co-glycolic acid) (PLGA) NPs with different surface coating or conjugation chemistries. Liquid chromatography-mass spectrometry-based metabolic profiling was performed on the extracts (n = 6) of the differentiated THP-1 cells treated with plain, Pluronic (F-127, F-68, and P-85)-coated and PEG-PLGA NPs and control (no treatment). Principal component analysis and orthogonal partial least squares-discriminant analysis (OPLS-DA) in conjunction with univariate and pathway analyses were performed to identify significantly changed metabolites and pathways related to exposure of the cells to NPs. OPLS-DA of each class in the study compared to the control showed clear separation and clustering with cross-validation values of R2 and Q2 > 0.5. A total of 105 metabolites and lipids were found to be significantly altered in the differentiated THP-1 cell profiles due to the NP exposure, whereas more than 20 metabolic pathways were found to be affected. These pathways included glycerophospholipid, sphingolipid, linoleic acid, arginine and proline, and alpha-linolenic acid metabolisms. PLGA NPs were found to perturb some amino acid metabolic pathways and altered membrane lipids to a different degree. The metabolic effect of the PLGA NPs on the cells were comparable to those caused by silver oxide NPs and other inorganic nanomaterials. However, PEG-PLGA NPs demonstrated a reduced impact on the cellular metabolism compared to Pluronic copolymer-coated PLGA and plain PLGA NPs.

Citation

Al-Natour, M. A., Abdelrazig, S., Ghaemmaghami, A. M., Alexander, C., & Kim, D. H. (2022). Metabolic Signatures of Surface-Modified Poly(lactic- co-glycolic acid) Nanoparticles in Differentiated THP-1 Cells Derived with Liquid Chromatography-Mass Spectrometry-based Metabolomics. ACS Omega, https://doi.org/10.1021/acsomega.2c01660

Journal Article Type Article
Acceptance Date Aug 3, 2022
Online Publication Date Aug 12, 2022
Publication Date Aug 12, 2022
Deposit Date Aug 19, 2022
Publicly Available Date Aug 22, 2022
Journal ACS Omega
Electronic ISSN 2470-1343
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1021/acsomega.2c01660
Keywords General Chemical Engineering; General Chemistry
Public URL https://nottingham-repository.worktribe.com/output/9906883
Publisher URL https://pubs.acs.org/doi/10.1021/acsomega.2c01660

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