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

Bio–nano interactions are a promising area of research, focused particularly on the interactions between proteins and nanomaterials (NMs). These interactions lead to the formation of the protein corona, a layer of proteins adsorbed to the surface of NMs; this corona determines the way in which cells within organisms “recognise” and interact with NMs. Corona formation has proven critical for cellular uptake, intracellular localization and toxicity arising from NMs. However, a major class of biological chemicals have been overlooked in the efforts to understand and predict the interactions of NMs with living organisms, namely metabolites, which are also involved in signaling cascades and toxic responses in biological systems. To date, very few studies have investigated this aspect of the NM corona, with initial work focusing upon the use of carbon nanotubes to clean persistent organic pollutants from contaminated air or water. As the protein corona field grew, limited interest in the metabolite corona began to emerge with investigations into the lipid composition of the corona around inhaled NMs and eventually more holistic analyses of the metabolite corona. We suggest that the metabolite corona co-exists with the protein one, since these smaller molecules can fit in between proteins, and indeed are often bound into protein complexes. We hypothesize that metabolites influence NMs impacts on molecular signaling and adverse outcome pathways. We show initial evidence that the metabolite corona is complementary to protein coronas, following similar rules of adsorption based on abundance and affinity leading to metabolite fingerprints akin to protein fingerprints. This work aims to highlight the metabolite corona as an important, but as yet greatly under represented, area of bio–nano interaction research, and encourage researchers to explore this aspect of the interactions between NMs and their surrounding biological environments.