Biological Identity of Nanoparticles In Vivo: Clinical Implications of the Protein Corona

Despite the advances in biomedical applications of nanoparticle (NP) and numerous publications, few NPs have made it to clinical trials and even fewer have reached clinical practice. This wide gap between bench discoveries and clinical applications is mainly because of our limited understanding of the biological identity of NPs. In physiological environments, NPs are coated by a 'protein corona' (PC), critically affecting physiological and therapeutic responses. To date, nearly all studies attempting to characterize the PC have been conducted in vitro. Here, we review recent advances in our understanding of the in vivo PC. We also discuss recent developments of quantitative models to predict biological interactions and how they offer new opportunities for the clinical translation of NPs.