A strategy for grouping of nanomaterials based on key physico-chemical descriptors as a basis for safer-by-design NMs

SummaryThere is an urgent need to establish a fundamental understanding of the mechanisms of nanomaterial (NM) interaction with living systems and the environment, in order for regulation of NMs to keep pace with their increasing industrial application. Identification of critical properties (physicochemical descriptors) that confer the ability to induce harm in biological systems is crucial, enabling both prediction of impacts from related NMs (via quantitative nanostructure–activity relationships (QNARs) and read-across approaches) and development of strategies to ensure these features are avoided or minimised in NM production in the future (“safety by design”). A number of challenges to successful implementation of such a strategy exist, including: (i) the lack of widely available systematically varied libraries of NMs to enable generation of sufficiently robust datasets for development and validation of QNARs; (ii) the fact that many physicochemical properties of pristine NMs are inter-related and thus cannot be varied systematically in isolation from others (e.g. increasing surface charge may impact on hydrophobicity, or changing the shape of a NM may introduce defects or alter the atomic configuration of the surface); and (iii) the effect of ageing, transformation and biomolecule coating of NMs under environmental or biological conditions.A novel approach to identify interlinked physicochemical properties, and on this basis identify overarching descriptors (axes or principle components) which can be used to correlate with toxicity is proposed. An example of the approach is provided, using three principle components which we suggest can be utilised to fully describe each NM, these being the intrinsic (inherent) properties of the NM, composition (which we propose as a separate parameter) and extrinsic properties (interaction with media, molecular coronas etc.)

Environmental context determines the impact of titanium oxide and silver nanoparticles on the functioning of intertidal microalgal biofilms

Coastal environments are receiving habitats for most nanoparticle (NP) waste. Coastal sediments, into which NPs accumulate, support microalgal biofilms that provide important ecosystem processes: primary production, enhanced sediment stabilisation, and nutrient recycling. We assessed the impact of realistic concentrations of titanium oxide (TiO₂) and silver (Ag) NPs on marine microalgal biofilms and associated ecosystem processes in simulated natural conditions, by exposing natural biofilms to TiO₂ and Ag-NPs for one-month periods in outdoor tidal mesocosms under three contrasted environmental contexts (seasons). Ag-NPs had no significant effects on microalgal biomass, sediment biostabilisation potential and sediment–water oxygen and nutrient fluxes, even at concentrations (25 μg l¯¹) higher than current estimated levels (25 ng l¯¹). TiO₂-NPs had no significant effect at current expected concentrations (25 μg l¯¹), but higher concentrations (25 mg l¯¹) resulted in decreased microalgal biomass; decreased ability of biofilms to biostabilise sediment, therefore limiting their coastal protection potential; reduced primary production and modified nutrient recycling. TiO₂-NPs impacts were dependent on the environmental context: most effect was seen in winter, while no toxicity on biofilms was demonstrated in early spring. Our findings demonstrate that while Ag-NPs, being liable to dissolution into Ag+ ions under the conditions tested, are not expected to have an environmental impact if current predictions of environmental loading prevail, TiO₂-NPs may have ecological consequences in coastal environments in addition to direct impacts on microbial biomass

A nanoinformatics decision support tool for the virtual screening of gold nanoparticle cellular association using protein corona fingerprints

The increasing use of nanoparticles (NPs) in a wide range of consumer and industrial applications has necessitated significant effort to address the challenge of characterizing and quantifying the underlying nanostructure – biological response relationships to ensure that these novel materials can be exploited responsibly and safely. Such efforts demand reliable experimental data not only in terms of the biological dose-response, but also regarding the physicochemical properties of the NPs and their interaction with the biological environment. The latter has not been extensively studied, as a large surface to bind biological macromolecules is a unique feature of NPs that is not relevant for chemicals or pharmaceuticals, and thus only limited data have been reported in the literature quantifying the protein corona formed when NPs interact with a biological medium and linking this with NP cellular association/uptake. In this work we report the development of a predictive model for the assessment of the biological response (cellular association, which can include both internalized NPs and those attached to the cell surface) of surface-modified gold NPs, based on their physicochemical properties and protein corona fingerprints, utilizing a dataset of 105 unique NPs. Cellular association was chosen as the end-point for the original experimental study due to its relevance to inflammatory responses, biodistribution, and toxicity in vivo. The validated predictive model is freely available online through the Enalos Cloud Platform (http://enalos.insilicotox.com/NanoProteinCorona/) to be used as part of a regulatory or NP safe-by-design decision support system. This online tool will allow the virtual screening of NPs, based on a list of the significant NP descriptors, identifying those NPs that would warrant further toxicity testing on the basis of predicted NP cellular association.</p