Understanding nano–bio interactions for safer material design
What happens when an allergen encounters the surface of a nanomaterial? The answer is more complex than simple adsorption. At the nano–bio interface, proteins can change their orientation, structure and accessibility — potentially altering the way they are recognised and processed by the immune system.
In their 2026 special report “Lessons learned from allergen adsorption on engineered nanomaterials: bridging experimental insights and computational technologies,” Xintong Chen and colleagues from PINK consortium partners Paris Lodron University Salzburg (Laura Schmitz, Mark Geppert, Sabine Hofer, Norbert Hofstätter, Martin Himly) and the University of Birmingham (Litty Johnson) examine current knowledge about these interactions. Their analysis connects experimental immunology with computational approaches and highlights implications for both nanomaterial safety and therapeutic applications.
A new biological identity at the surface
When nanomaterials enter a biological environment, proteins can adsorb onto their surfaces and form a protein corona. Its composition and structure depend strongly on properties such as particle size, surface charge, hydrophobicity, morphology, porosity and agglomeration state, as well as environmental conditions.
For allergens, this interaction can have important consequences. Adsorption may stabilise or destabilise the protein, cause partial unfolding or other conformational changes, and modify the accessibility of immunologically relevant epitopes.
As the authors summarise:
“Allergen adsorption onto NMs reshapes how the immune system perceives and processes these proteins.”
This means that the immune system may effectively encounter something different from the original allergen.
One interaction – very different outcomes.
Importantly, allergen–nanomaterial interactions are not inherently beneficial or harmful. Their immunological consequences depend on the particular nanomaterial and allergen, their interaction, and the conditions of exposure.
Adsorption can hide existing IgE-binding epitopes, expose or generate new epitopes, alter cellular uptake and change how allergens are proteolytically processed and presented to immune cells. These mechanisms are illustrated particularly clearly in Figure 1 on page 996, where the authors show six possible effects along the pathway from adsorption to altered T-cell activation.
Consequently, nanomaterials can act as unintended adjuvants and potentially enhance allergic sensitisation and inflammation. Under other conditions, however, deliberately engineered nanomaterial–allergen complexes can promote immune tolerance and provide platforms for allergen-specific immunotherapy.
“Allergen adsorption onto NMs can either enhance allergic sensitization or promote immunological tolerance, depending on the NM and allergen properties.”
This dual behaviour makes understanding the nano–bio interface important both for risk assessment and therapeutic design.
Bridging experiments and computational technologies
A central message of the report is that individual experimental assays cannot capture the complete biological complexity involved. Dose, exposure route and exposure kinetics matter, as do physiological barriers, protein-corona dynamics and interactions among different immune-cell populations. Computational approaches can help bridge some of these gaps. Molecular docking and molecular dynamics simulations can provide mechanistic information about binding sites, adsorption energetics and structural changes. Adverse Outcome Pathway approaches can help connect molecular interactions with subsequent biological effects. One particularly important concept discussed by the authors is dose bridging: computational methods can help translate realistic environmental or occupational exposure into effective doses appropriate for in vitro experiments.
“Integrating experimental-computational workflows for dose finding is therefore essential for NM immunotoxicity testing, interpretation of results and significance assignment.”
Why this matters for PINK
This integration of experimental evidence, mechanistic understanding and computational prediction connects closely with the scientific approach of PINK. SSbD requires more than identifying whether a material produces a biological effect under a particular experimental condition. It requires understanding which material properties drive that effect, under which exposure conditions, through which biological mechanisms, and with what degree of confidence.
Allergen–nanomaterial interactions provide an instructive example. Surface chemistry, size and morphology influence adsorption; adsorption changes the biological identity of the interface; and these changes can propagate towards different immunological outcomes. Computational models and New Approach Methodologies can help connect these different levels of information and ultimately support earlier and better-informed material-design decisions.
From understanding interactions to designing safer materials
The authors identify important remaining challenges, including variability between nanomaterial batches and allergens, insufficient standardisation, limited chronic-exposure and in vivo data, and the need for more predictive models. More physiologically realistic experimental systems such as co-cultures, organoids and organs-on-chip could help close some of these gaps.
Looking ahead, the report envisages closer integration of advanced experimental models with computational approaches. This could not only improve assessment of unintended allergen interactions but also allow nano–bio interactions to be deliberately engineered for therapeutic purposes. Ultimately, the lesson extends beyond allergy: understanding what happens at the interface between an advanced material and its biological environment is an important component of designing materials that are safe from the outset.
The research was supported by the EU Horizon Europe PINK project (Grant Agreement No. 101137809) and if you are interested in reading the full publication follow this link.
