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Nanoparticle Protein Coronas Differentially Interrogate Proteomes with Superior Performance Compared to Conventional Deep Proteome Workflows

ABSTRACT: The superior performance of a multiple NP workflow was shown compared to high-complexity, state-of-the-art, high-pH fractionation strategies in terms of depth and precision. We also evaluate the link between the physicochemical properties of NPs and their differential protein selectivity.

INSTRUMENT(S): Orbitrap Fusion Lumos, TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Theo Platt

LAB HEAD: Omid C. Farokhzad

PROVIDER: PXD022285 | Pride | 2022-02-24

REPOSITORIES: Pride

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Engineered nanoparticles enable deep proteomics studies at scale by leveraging tunable nano-bio interactions.

Ferdosi Shadi S Tangeysh Behzad B Brown Tristan R TR Everley Patrick A PA Figa Michael M McLean Matthew M Elgierari Eltaher M EM Zhao Xiaoyan X Garcia Veder J VJ Wang Tianyu T Chang Matthew E K MEK Riedesel Kateryna K Chu Jessica J Mahoney Max M Xia Hongwei H O'Brien Evan S ES Stolarczyk Craig C Harris Damian D Platt Theodore L TL Ma Philip P Goldberg Martin M Langer Robert R Flory Mark R MR Benz Ryan R Tao Wei W Cuevas Juan Cruz JC Batzoglou Serafim S Blume John E JE Siddiqui Asim A Hornburg Daniel D Farokhzad Omid C OC

Proceedings of the National Academy of Sciences of the United States of America 20220311 11

SignificanceDeep profiling of the plasma proteome at scale has been a challenge for traditional approaches. We achieve superior performance across the dimensions of precision, depth, and throughput using a panel of surface-functionalized superparamagnetic nanoparticles in comparison to conventional workflows for deep proteomics interrogation. Our automated workflow leverages competitive nanoparticle-protein binding equilibria that quantitatively compress the large dynamic range of proteomes to a ...[more]

PMID: 35275789

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Nanoparticle Protein Coronas Differentially Interrogate Proteomes with Superior Performance Compared to Conventional Deep Proteome Workflows

Project description:The superior performance of a multiple NP workflow was shown compared to high-complexity, state-of-the-art, high-pH fractionation strategies in terms of depth and precision. We also evaluate the link between the physicochemical properties of NPs and their differential protein selectivity.

2022-02-24 | PXD028634 | Pride

Molecular mechanisms underlying zinc oxide nanoparticle induced insulin resistance in mice

Project description:Zinc oxide nanoparticles (ZnO NPs) represent an important class of commercially applied materials. Recently, adverse effects of ZnO NPs were found in humans and animals following ingestion, although the effects on endocrine system disease remain unclear. In this study, ZnO NPs were orally administered to mice, and at doses of 25 mg/kg bw (body weight) ZnO NPs and above, plasma glucose increased significantly. The genome-wide effects of ZnO NPs were then investigated using RNA-sequencing technology. In the cluster analysis, the most significantly enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways concerned membranes and their close association with endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation. Biochemical and gene and protein expression analyses revealed that ZnO NPs activated a xenobiotic biodegradation response and increased the expression of cytochrome P450 (CYP) enzymes in mice livers, leading to ER stress. The ER stress increased ROS generation. The high levels of ROS activated the MAPK and NF-B pathways and induced an inflammation response, resulting in the phosphorylation of insulin receptor substrate 1. Thus, the insulin resistance that developed was the primary mechanism for the increase in the plasma glucose of mice treated orally with ZnO NPs.

2022-08-20 | GSE136174 | GEO

Identified small open reading frame encoded peptides in plasma with nanoparticle protein coronas

Project description:We identified small open reading frames encoded peptided in human serum with nanoparticle protein coronas method using mass spectrometry. Four nanoparticle material treatments (TiO2, Fe3O4@SiO2, Fe3O4@SiO2@TiO2, NPs-mix), ACN and untreated control were performed with triplicates. The comparision of 96 well plate and centrifuge tube was carried out with 6 replicates and 4 replicates respectively.

2023-05-24 | PXD042459 | iProX

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

Project description: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.

2022-04-27 | MSV000089322 | MassIVE

Regulating Protein Corona Formation and Dynamic Protein Exchange by Controlling Nanoparticle Hydrophobicity

Project description:Physiochemical properties of engineered nanoparticles (NPs) play a vital role in nano-bio interactions, which are critical for nanotoxicity and nanomedicine research. To understand the effects of NP hydrophobicity on the formation of the protein corona, we synthesized four gold NPs with a continuous change in hydrophobicity ranging from -2.6 to 2.4. Hydrophobic NPs adsorbed 2.1-fold proteins compared to hydrophilic ones. Proteins with small molecular weights (< 50 kDa) and negatively charge (PI < 7) constituted the majority of the protein corona, especially for hydrophobic NPs. Moreover, proteins preferred binding to hydrophilic NPs (vitronectin and antithrombin III), hydrophobic NPs (serum albumin and hemoglobin fetal subunit beta), and medium hydrophobic NPs (talin 1 and prothrombin) were identified. Besides, proteins such as apolipoprotein bound to all NPs, did not show surface preference. We also found that there was a dynamic exchange between hard protein corona and solution proteins. Because of such dynamic exchanges, protein-bound NPs could expose their surface in biological systems. Hydrophilic NPs exhibited higher protein exchange rate than hydrophobic NPs. Above understandings have improved our capabilities to modulate protein corona formation by controlling surface chemistry of NPs. These will also help modulate nanotoxicity and develop better nanomedcines.

2020-02-24 | PXD017429 | Pride

Nuclease-resistant DNA via high-density packing in polymeric micellar nanoparticle coronas.

Project description: Not available

| S-EPMC3608424 | biostudies-literature

BEAS2B cells and A549 cells: control versus nanoparticle exposure

Project description:Fragmentary knowledge exists on the adverse health effects of CoO- and CeO2-nanoparticles (NP)s. We analyzed toxicogenomic profiles of BEAS-2B versus A549 cells using genome-wide transcriptomics to identify molecules and cellular processes that are triggered by monodispersed noncytotoxic suspensions of 7-nm CoO- and 4-nm CeO2-NPs for 3, 6, 10, and 24 hours. We aimed to investigate 1) whether a cell type responds similarly to two different NPs exposure, 2) whether alveolar versus bronchial epithelial cells respond differently to the same NP, and 3) whether immune processes are influenced. The kinetics of the cell responses induced by the two NPs were different between the two lung epithelial cell models. Both CoO- and CeO2-NP exposure induced mainly downregulation of gene transcription. BEAS-2B cells were found to be more sensitive towards NP exposure, as they showed a higher total number of differentially expressed transcripts (DET) at a 10-fold lower NP-concentration than A549 cells. Hierarchical clustering of all DET indicated that the transcriptional responses were quite heterogeneous among the two cell types and two NPs. Between 1% and 14% DET encoding markers involved in immune system processes were observed in the BEAS-2B and A549 cell lines, with the highest fractions observed in BEAS-2B cells. Most of these genes, i.e. ITGB2, TLR6, PAG1, HLA-DRB3, TIRAP, and HLA-A, are involved in immune signalling. The AKT1 gene, which showed persistently decreased expression levels, was identified as a possible generic marker of lung epithelial cell-NP interaction. Our data suggest that CoO- and CeO2-NPs give rise to distinct responses.

2014-12-01 | GSE45763 | GEO

Dynamic protein coronas revealed as a modulator of silver nanoparticle sulphidation in vitro.

Project description: Not available

| S-EPMC4906166 | biostudies-literature

MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins (Human exosome, LDL, and HDL miRNA Signatures)

Project description:Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that human high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Highly-purified fractions of human HDL contain small RNAs, and the HDL-miRNA profile from normal subjects is significantly different than familial hypercholesterolemia subjects. miRNAs were demonstrated to associate with both native and reconstituted HDL particles, and reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. Furthermore, HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of mRNA reporters. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations suggest that HDL participates in a novel mechanism of intercellular communication involving the transport and delivery of miRNAs. Human exosome, LDL, and HDL miRNA Signatures Profiled miRNA signatures from exosome, LDL, HDL in same subject

2011-03-23 | E-GEOD-25149 | biostudies-arrayexpress

MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins

Project description:This SuperSeries is composed of the following subset Series: GSE25108: MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins (Human HDL miRNA Signatures) GSE25110: MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins (Human HDL and Exosome miRNA Signatures) GSE25149: MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins (Human exosome, LDL, and HDL miRNA Signatures) GSE25150: MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins (Mouse HDL signatures from WT and LDLR-/- high fat diet) GSE25311: MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins (HG-U133 2.0) GSE25424: MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins (microRNA signatures retrieved from rHDL injected into WT, ApoE-/- chow, ApoE-/-high fat diet) Refer to individual Series

2011-04-03 | E-GEOD-25425 | biostudies-arrayexpress

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