The nanoparticle biomolecule corona: lessons learned - challenge accepted?

Besides the wide use of engineered nanomaterials (NMs) in technical products, their applications are not only increasing in biotechnology and biomedicine, but also in the environmental field. While the physicochemical properties and behaviour of NMs can be characterized accurately under idealized conditions, this is no longer the case in complex physiological or natural environments. Herein, proteins and other biomolecules rapidly bind to NMs, forming a protein/biomolecule corona that critically affects the NMs' (patho) biological and technical identities. As the corona impacts the in vitro and/or in vivo NM applications in humans and ecosystems, a mechanistic understanding of its relevance and of the biophysical forces regulating corona formation is mandatory. Based on recent insights, we here critically review and present an updated concept of corona formation and evolution. We comment on how corona signatures may be linked to effects at the nano-bio interface in physiological and environmental systems. In order to comprehensively analyse corona profiles and to mechanistically understand the coronas' biological/ecological impact, we present a tiered multidisciplinary approach. To stimulate progress in this field, we introduce the potential impact of the corona for NM-microbiome-(human) host interactions and the novel concept of 'nanologicals', i.e., the nanomaterial-specific targeting of molecular machines. We conclude by discussing the relevant challenges that still need to be resolved in this field.