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
R
2
and
Q
2
> 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.