Metabolomic method to detect a metabolite corona on amino-functionalized polystyrene nanoparticles

Grintzalis, Konstantinos; Lawson, Thomas N.; Nasser, Fatima; Lynch, Iseult; Viant, Mark R.

doi:10.1080/17435390.2019.1577510

Cited by 31 publications

(32 citation statements)

References 32 publications

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“…Given the highly hydrophilic nature of the metabolite test mixtures, a three‐step washing procedure was considered, comprising two washing steps with water and one washing step with methanol/water (1:1, v/v). [ 50 ] All washing steps were assisted with sonication for 5 min in a water bath at room temperature.…”

Section: Resultsmentioning

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: Resultsmentioning

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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“…To date the focus has been on proteins (as biologically active agents) and NOM as a dispersant, but the myriad of small molecules (metabolites) present in biological organisms, many of which interact directly with proteins, are also likely to play important roles in how organisms process and respond to NMs. The first efforts to develop a methodology to characterize the small‐molecule corona secreted by D. magna have recently been published, and further studies are needed to understand the implications of the small molecule corona. Indeed, the ultimate goal is to understand the complete corona—the composition and interplay of all constituents in order to understand the true identity of NMs being exposed to organisms.…”

Section: Resultsmentioning

confidence: 99%

Nanomaterials in the Environment Acquire an “Eco‐Corona” Impacting their Toxicity to Daphnia Magna—a Call for Updating Toxicity Testing Policies

2019

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Nanomaterials (NMs) are particles with at least one dimension between 1 and 100 nm and a large surface area to volume ratio, providing them with exceptional qualities that are exploited in a variety of industrial fields. Deposition of NMs into environmental waters during or after use leads to the adsorption of an ecological (eco-) corona, whereby a layer of natural biomolecules coats the NM changing its stability, identity and ultimately toxicity. The eco-corona is not currently incorporated into ecotoxicity tests, although it has been shown to alter the interactions of NMs with organisms such as Daphnia magna (D. magna). Here, the literature on environmental biomolecule interactions with NMs is synthesized and a framework for understanding the eco-corona composition and its role in modulating NMs ecotoxicity is presented, utilizing D. magna as a model. The importance of including biomolecules as part of the current international efforts to update the standard testing protocols for NMs, is highlighted. Facilitating the formation of an eco-corona prior to NMs ecotoxicity testing will ensure that signaling pathways perturbed by the NMs are real rather than being associated with the damage arising from reactive NM surfaces "acquiring" a corona by pulling biomolecules from the organism's surface.novel and unique qualities that are not traditionally exhibited by bulk material of the same composition. NMs have been at the core of novel research for two decades and are incorporated into products spanning a range of industrial fields. For example, NMs properties are exploited in cancer research, such as the utilization of surface plasmon resonance properties of gold (Au) NMs; here the NMs are conjugated to antibodies complementary to antigens on cancer cells and are thereby internalized, following which oscillation of the Au electron cloud at a specific wavelength of light converts the absorbed light into localized heat to specifically destroy cancer cells. [1] Another example is exploitation of the antimicrobial properties of silver (Ag) NMs which undergo high dissolution to release Ag + ions [2] and where the dissolution site, rate (and thus toxicity) can be adjusted depending on the surface coating. [3] Considering that NMs are becoming so widely used, their release into the environment is inevitable. Despite this, considerably less research has focused on the implications of NMs on environmental organisms, especially under realistic conditions, than on development of their applications. NMs may enter freshwater systems from industrial effluent, where, for example, the concentrations of zinc oxide (ZnO) NMs, widely used in sunscreens and paints, in river waters has been found to be as high as 150 ng L −1 , [4] while gold (Au) NMs excreted following use in medical applications into surface waters have been predicted to be 470 pg L −1 [5] With deposition of NMs into environmental waters increasing, concerns regarding the potential for toxicity posed by NMs have demanded action, although the standard testing approaches h...

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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%

“…Many of these xenobiotics are known to still be biologically active in the environment and have been demonstrated to affect reproductive behavior and neurochemistry of fish to name just a single organism. [30][31][32][33][34] Metabolites have been confirmed to be present in aquatic organism secretions (e.g., daphnia conditioned medium), 35 while waste water treatment plants release thousands of tons of human waste including proteins and metabolites into rivers and oceans around the world. 36 There have been a number of proteomics studies of soils 37,38 and water columns 39 demonstrating that proteins are present in the wider environment.…”

Section: Introductionmentioning

confidence: 99%

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

Chetwynd

Lynch

2020

Environ. Sci.: Nano

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Metabolomic method to detect a metabolite corona on amino-functionalized polystyrene nanoparticles

Cited by 31 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

Nanomaterials in the Environment Acquire an “Eco‐Corona” Impacting their Toxicity to Daphnia Magna—a Call for Updating Toxicity Testing Policies

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

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