Nanotechnology represents a promising scientific field with broad applications and has attracted considerable investment over the past years. However, responsible and careful implementation of nanoscience innovations with continuous monitoring of the production process is imperative to ensure they do not pose harm to human health or the environment at any stage of their life-cycle. Seeking to facilitate this, the EU-funded Nanointeract project set out to create a scientific and technical basis for understanding and predicting the biological impacts of engineered nano-scale particles. The project sought to connect the uptake and biodistribution of nanoparticles by cells, as well as their effect on cellular function. More specifically, scientists established experimental protocols for studying nanoparticle interaction with cells, aquatic plants and organisms. Nanoparticle cellular uptake is believed to occur through proteins encountered in biological fluids, forming a biomolecular ‘corona’ on their surface. To understand how this nanoparticle capping affects their dose and dispersion evolution, the Nanointeract project devoted considerable effort to studying the reciprocal interplay between nanoparticles and proteins. The effect of the adsorbed protein on nanoparticle stability and the biological impact of nanoparticles on protein conformation and function were studied. Results indicated that blood plasma-derived coronas were sufficiently long-lived and were likely to be what the cell detected rather than the nanoparticle surface. Additionally, the nature of the protein corona determined the nanoparticle uptake by cells affecting their kinetics and localisation. Toxicology screening of the most widely used silicon dioxide (SiO2) nanoparticles from a range of different sources showed that, in general, they were not cytotoxic. However, long-term exposure to high concentrations of these nanoparticles could potentially result in particle accumulation and, subsequently, induce acute or chronic toxicity. Collectively, the findings of the Nanointeract initiative confirmed the necessity and importance of conducting nanosafety assessment, providing the first indications that the protein ‘corona’ should become incorporated into the nanoparticle characterisation process.