Nanoparticles for biomedical applications: exploring and exploiting molecular interactions at the nano-bio interface

Nanomaterials have high potential as powerful tools for nanomedicine in a wide range of most promising applications as highly specific devices for diagnosis and therapy. Yet, despite enormous research activities in the design and synthesis of nanomaterials for biomedicine, only a small number of those have made their way to clinical use. The unavoidable formation of a biomolecular adsorption layer, the 'protein corona' or 'biomolecular corona' around nanoparticles (NPs) has been recognized as a major roadblock on the way toward the efficient design of nanomedicines. It masks the generic NP properties and creates a new 'biological identity' that largely controls the interactions with the biological environment. Therefore, for successful design of nanomedical devices, researchers must anticipate formation of this protein adlayer and its ensuing effects. In this review, we summarize our current knowledge in the field and focus on three topics that appear to be important for furthering progress in our ability to predict in-vivo responses to NP incorporation from in-vitro studies. First, we address fundamental physicochemical issues of protein corona formation as revealed by recent in-vitro studies, with a focus on the underlying mechanistic details. Second, we illustrate with recent examples how our present, still incomplete understanding can already be exploited to control protein corona formation in the organism, including important processes involving the immune system. Third, recent advances in the transition from in-vitro to in-vivo studies of protein adsorption will be summarized, which is obviously a key step in NP development for nanomedicine. We conclude this review with an outlook on possible future developments in the field. (c) 2019 The Author(s). Published by Elsevier Ltd.