Identification and characterization of small organic compounds within the corona formed around engineered nanoparticles

Pink, Mario; Verma, Nisha; Kersch, Christian; Schmitz‐Spanke, Simone

doi:10.1039/c8en00161h

Cited by 27 publications

(32 citation statements)

References 32 publications

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“…Furthermore, a limited number of studies have investigated a broader range of metabolites and demonstrated that a wide array of metabolites can interact with NMs to form a metabolite corona. [ 26–29 ] Yet, the concept of a small molecule corona, or indeed the realization that the presence of metabolites within the protein corona may mediate the NM behavior, has been largely overlooked in nanosafety to date. Here, characterization of the selective adsorption of small molecules to NMs, forming a metabolite corona, and the impact of proteins on the composition of the small molecule corona are presented.…”

Section: Introductionmentioning

confidence: 99%

The Nanomaterial Metabolite Corona Determined Using a Quantitative Metabolomics Approach: A Pilot Study

Chetwynd

Zhang

Thorn³

et al. 2020

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Nanomaterials (NMs) are promptly coated with biomolecules in biological systems leading to the formation of the so‐called corona. To date, research has predominantly focused on the protein corona and how it affects NM uptake, distribution, and bioactivity by conferring a biological identity to NMs enabling interactions with receptors to mediate cellular responses. Thus, protein corona studies are now integral to nanosafety assessment. However, a larger class of molecules, the metabolites, which are orders of magnitude smaller than proteins (<1000 Da) and regulate metabolic pathways, has been largely overlooked. This hampers the understanding of the bio–nano interface, development of computational predictions of corona formation, and investigations into uptake or toxicity at the cellular level, including identification of molecular initiating events triggering adverse outcome pathways. Here, a capillary electrophoresis–mass spectrometry based metabolomics approach reveals that pure polar ionogenic metabolite standards differentially adsorb to a range of 6 NMs (SiO2, 3 TiO2 with different surface chemistries, and naïve and carboxylated polystyrene NMs). The metabolite corona composition is quantitatively compared using protein‐free and complete plasma samples, revealing that proteins in samples significantly change the composition of the metabolite corona. This key finding provides the basis to include the metabolite corona in future nanosafety endeavors.

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Section: Introductionmentioning

confidence: 99%

The Nanomaterial Metabolite Corona Determined Using a Quantitative Metabolomics Approach: A Pilot Study

Chetwynd

Zhang

Thorn³

et al. 2020

Small

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“…The second, more direct, approach is to elute the metabolites from the NMs, as is done for protein corona analysis. 35,88 There are a number of possible ways to do this, many of which have been applied in the metabolomics community to isolate metabolites from tissues or biofluids. [89][90][91] The most likely to work are successive washes in solvents ranging from the polar, such as water, to the less polar solvents such as methanol and hexane.…”

Section: Isolation Of the Metabolite Coronamentioning

confidence: 99%

“…It is also likely that varying the pH of the solvent would have a significant effect on the elution of metabolites, either through hydrolysis of any bonds or changing the charge status of either the metabolite, NM or NM surface ligands thus releasing the metabolites. 88 It may also be possible to dissolve the NM if the right pH and material is being used. 96 Each NM and surface modified NM will require optimization of the metabolite corona isolation method, although general rules may emerge.…”

Section: Isolation Of the Metabolite Coronamentioning

confidence: 99%

“…124 To date, this approach has been used once for the metabolite corona around 4 metal oxide NMs. 88 4.2.3 Capillary electrophoresis-mass spectrometry (CE-MS). CE is a technology that has been used in colloid, particle and nanoscience labs for around 3 decades to characterise the size, surface charge and zeta potential of (nano)particles and has started to find a role in protein corona characterisation.…”

Section: Liquid Chromatography-mass Spectrometry (Lc-ms) Lc-ms Is Thmentioning

confidence: 99%

“…Pink et al 88 carried out extensive method development to isolate, derivatise, separate and detect 200 metabolite features from CuO, ZrO 2 , TiO 2 , ZnO and carbon black NMs incubated with cell culture medium and simulated lung fluid. Of the 200 features detected, 69% could be annotated based upon their retention index, mass and fragmentation patterns.…”

Section: Untargeted Analysis Of the Metabolite Coronamentioning

confidence: 99%

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The rise of the nanomaterial metabolite corona, and emergence of the complete corona

Chetwynd

Lynch

2020

Environ. Sci.: Nano

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Formation of a protein corona on the surface of extracellular vesicles in blood plasma

Tóth

Turiák

Visnovitz

et al. 2021

J of Extracellular Vesicle

215

227

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In this study we tested whether a protein corona is formed around extracellular vesicles (EVs) in blood plasma. We isolated medium‐sized nascent EVs of THP1 cells as well as of Optiprep‐purified platelets, and incubated them in EV‐depleted blood plasma from healthy subjects and from patients with rheumatoid arthritis. EVs were subjected to differential centrifugation, size exclusion chromatography, or density gradient ultracentrifugation followed by mass spectrometry. Plasma protein‐coated EVs had a higher density compared to the nascent ones and carried numerous newly associated proteins. Interactions between plasma proteins and EVs were confirmed by confocal microscopy, capillary Western immunoassay, immune electron microscopy and flow cytometry. We identified nine shared EV corona proteins (ApoA1, ApoB, ApoC3, ApoE, complement factors 3 and 4B, fibrinogen α‐chain, immunoglobulin heavy constant γ2 and γ4 chains), which appear to be common corona proteins among EVs, viruses and artificial nanoparticles in blood plasma. An unexpected finding of this study was the high overlap of the composition of the protein corona with blood plasma protein aggregates. This is explained by our finding that besides a diffuse, patchy protein corona, large protein aggregates also associate with the surface of EVs. However, while EVs with an external plasma protein cargo induced an increased expression of TNF‐α, IL‐6, CD83, CD86 and HLA‐DR of human monocyte‐derived dendritic cells, EV‐free protein aggregates had no effect. In conclusion, our data may shed new light on the origin of the commonly reported plasma protein ‘contamination’ of EV preparations and may add a new perspective to EV research.

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Identification and characterization of small organic compounds within the corona formed around engineered nanoparticles

Abstract: The biological identity of nanoparticles depends on the organic compounds bound to the surface; however, compounds other than proteins are largely uninvestigated. This study highlights the presence of unique compound profiles within the corona of the tested nanoparticles.

Cited by 27 publications

References 32 publications

The Nanomaterial Metabolite Corona Determined Using a Quantitative Metabolomics Approach: A Pilot Study

The Nanomaterial Metabolite Corona Determined Using a Quantitative Metabolomics Approach: A Pilot Study

The rise of the nanomaterial metabolite corona, and emergence of the complete corona

Formation of a protein corona on the surface of extracellular vesicles in blood plasma

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