The emergence of nanoinformatics as a key component of nanotechnology and nanosafety assessment for the prediction of engineered nanomaterials (NMs) properties, interactions, and hazards, and for grouping and read-across to reduce reliance on animal testing, has put the spotlight firmly on the need for access to high-quality, curated datasets. To date, the focus has been around what constitutes data quality and completeness, on the development of minimum reporting standards, and on the FAIR (findable, accessible, interoperable, and reusable) data principles. However, moving from the theoretical realm to practical implementation requires human intervention, which will be facilitated by the definition of clear roles and responsibilities across the complete data lifecycle and a deeper appreciation of what metadata is, and how to capture and index it. Here, we demonstrate, using specific worked case studies, how to organise the nano-community efforts to define metadata schemas, by organising the data management cycle as a joint effort of all players (data creators, analysts, curators, managers, and customers) supervised by the newly defined role of data shepherd. We propose that once researchers understand their tasks and responsibilities, they will naturally apply the available tools. Two case studies are presented (modelling of particle agglomeration for dose metrics, and consensus for NM dissolution), along with a survey of the currently implemented metadata schema in existing nanosafety databases. We conclude by offering recommendations on the steps forward and the needed workflows for metadata capture to ensure FAIR nanosafety data.

Nanotechnology is a fast growing field and already a multi-billion dollar market with numerous consumer products.

An allergen–nanoparticle interaction study was performed using hAELVi cells grown under submerged vs. air–liquid interface culture conditions. Choice of cellular models showed impact on the investigation of uptake kinetics and inflammatory responses.

The innate immune system evolved to detect and react against potential dangers such as bacteria, viruses, and environmental particles. The advent of modern technology has exposed innate immune cells, such as monocytes, macrophages, and dendritic cells, to a relatively novel type of particulate matter, i.e., engineered nanoparticles. Nanoparticles are not inherently pathogenic, and yet cases have been described in which specific nanoparticle types can either induce innate/inflammatory responses or modulate the activity of activated innate cells. Many of these studies rely upon activation by agonists of toll-like receptors, such as lipopolysaccharide or peptidoglycan, instead of the more realistic stimulation by whole live organisms. In this review we examine and discuss the effects of nanoparticles on innate immune cells activated by live bacteria. We focus in particular on how nanoparticles may interfere with bacterial processes in the context of innate activation, and confine our scope to the effects due to particles themselves, rather than to molecules adsorbed on the particle surface. Finally, we examine the long-lasting consequences of coexposure to nanoparticles and bacteria, in terms of potential microbiome alterations and innate immune memory, and address nanoparticle-based vaccine strategies against bacterial infection.

The immune system is professional in recognizing and responding to non-self, including nanomaterials. Immune responses by professional and nonprofessional immune cells are thus nearly inevitable upon exposure of cells and organisms to such materials. The state of research into taking the immune system into account in nanosafety studies is reviewed and three aspects in which further improvements are desirable are identified: 1) Due to technical limitations, more stringent testing for endotoxin contamination should be made. 2) Since under overdose conditions immunity shows unphysiological responses, all doses used should be justified by being equivalent to tissue-delivered doses. 3) When markers of acute inflammation or cell stress are observed, functional assays are necessary to distinguish between homeostatic fluctuation and genuine defensive or tolerogenic responses. Since immune activation can also indicate that the immune system considers a stimulus to be harmless and induces tolerance, activation markers by themselves do not necessarily imply a danger to the body. Guidelines such as these are necessary to approach the point where specific nanomaterials are classified as safe based on reliable testing strategies.

Nanomaterials have found extensive interest in the development of novel vaccines, as adjuvants and/or carriers in vaccination platforms. Conjugation of protein antigens at the particle surface by non-covalent adsorption is the most widely used approach in licensed particulate vaccines. Hence, it is essential to understand proteins’ structural integrity at the material interface in order to develop safe-by-design nanovaccines. In this study, we utilized two model proteins, the wild-type allergen Bet v 1 and its hypoallergenic fold variant (BM4), to compare SiO2 nanoparticles with Alhydrogel® as particulate systems. A set of biophysical and functional assays including circular dichroism spectroscopy and proteolytic degradation was used to examine the antigens’ structural integrity at the material interface. Conjugation of both biomolecules to the particulate systems decreased their proteolytic stability. However, we observed qualitative and quantitative differences in antigen processing concomitant with differences in their fold stability. These changes further led to an alteration in IgE epitope recognition. Here, we propose a toolbox of biophysical and functional in vitro assays for the suitability assessment of nanomaterials in the early stages of vaccine development. These tools will aid in safe-by-design innovations and allow fine-tuning the properties of nanoparticle candidates to shape a specific immune response.

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

The utility of decision-making tools for the risk governance of nanotechnology is at the core of this paper. Those working in nanotechnology risk management have been prolific in creating such tools, many derived from European FP7 and H2020-funded projects. What is less clear is how such tools might assist the overarching ambition of creating a fair system of risk governance. In this paper, we reflect upon the role that tools might and should play in any system of risk governance. With many tools designed for the risk governance of this emerging technology falling into disuse, this paper provides an overview of extant tools and addresses their potential shortcomings. We also posit the need for a data readiness tool. With the EUs NMP13 family of research consortia about to report to the Commission on ways forward in terms of risk governance of this domain, this is a timely intervention on an important element of any risk governance system.