Modulation of Pulmonary Toxicity in Metabolic Syndrome due to Variations in Nanoparticle-Biocorona Composition

ABSTRACT: Following introduction into a biological environment, nanoparticles (NPs) interact with biomolecules forming a biocorona (BC) on their surface altering cell interactions and toxicity. Metabolic syndrome (MetS) is a prevalent condition and enhances susceptibility to inhaled exposures. We hypothesize distinct NP-biomolecule interactions occur in the lungs due to MetS resulting in the formation of unique NP-BCs contributing to enhanced toxicity. Bronchoalveolar lavage fluid (BALF) was collected from healthy and MetS mouse models and used to evaluate variations in the BC formation on 20 nm iron oxide NPs. NPs without or with BCs were characterized for hydrodynamic size and zeta potential. Protein and lipid components of the BCs were evaluated via proteomic and lipidomic assessments. Unique biomolecules were determined to associate with iron oxide NPs while shared biomolecules demonstrated differential abundance based on disease state. A mouse macrophage cell line was utilized to examine alterations in cell interactions and toxicity due to BCs. Exposures for 1h or 24h with NPs did not demonstrate overt cytotoxicity. Darkfield microscopy and X-ray fluorescence (XRF) analysis determined enhanced iron oxide NP internalization due to the MetS BC compared to the healthy BC. Macrophages exposed to NPs with a MetS-BC for 1h or 24h demonstrated enhanced gene expression of inflammatory markers CCL2, IL-6, and TNF-alpha compared to ion oxide NPs with a healthy BC. Inflammatory pathways were examined by western blots to determine activation of specific proteins within the MAP kinase, Jak-Stat, and NF- kB signaling pathways. Activation of STAT3, NF-kB, and ERK pathways were determined to be upregulated due to the MetS-BC. Specifically, the Jak-Stat pathway was determined to be the most upregulated inflammatory pathway following exposure to NPs with a MetS BC.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Jonathan H. Shannahan  

PROVIDER: MSV000089322 | MassIVE | Wed Apr 27 12:33:00 BST 2022

REPOSITORIES: MassIVE