Of Mice, Men and Nanoparticle Biocoronas: Are In Vitro to In Vivo Correlations and Interspecies Extrapolations Realistic?

Abstract

A great deal of research on the potential bio­ logical effects and biodistribution of nano­ materials in humans are inferred from in vitro cell culture studies or in vivo rodent models. A common theme emerging in predicting nanoparticle biological effects is the role of the protein corona. However, to link these data to what occurs in humans requires the use of extrapolation techniques that take into account species­specific physiology, such as the basal metabolic rate that drives most biodis­ tribution and elimination processes. Forma­ tion and stabilization of nanoparticle protein coronas are independent of these physiological rates, making simple extrapolations theoreti­ cally problematic. Similarly, if nanoparticle biocorona complexes determine in vivo bio­ distribution, how does one extrapolate in vitro cell culture data, where coronas may be fun­ damentally different or even absent, to in vivo data, where they are deterministic. Currently, simple extrapolation strategies used in phar­ macology and toxicology studies cannot com­ pensate for these processes. The development of mechanistic physiologically based pharma­ cokinetic models could incorporate these pro­ cesses if appropriate data were available. These issues have not been adequately considered by the nanomedicine or nanotoxicology commu­ nity, and are even ignored in current risk assess­ ment paradigms, yet are crucial for making biologically meaningful extrapolations. Recent research has made the formation of nanoparticle protein coronas an essen­ tial component in describing nanoparticle biodistribution in the body [1–3]. This has long been recognized to occur with particle opsonization and has been a major factor driving pharmaceutical strategies to avoid this process (e.g., PEGylation) [4]. However, the latest studies have described a more complex