Kinetics and Timescales in Bio–Nano Interactions

Abstract

Engineered nanoparticles (NPs) have the potential to revolutionize disease diagnostics and treatment. However, NP interactions with proteins in biological fluids complicate their in vivo control. These interactions often lead to the formation of protein coronas around the NP surface, shaping NP fate and behavior within biological systems. To harness the full potential of NPs in biomedical applications, it is therefore essential to gain a comprehensive understanding of their interactions with proteins. Within this context, it must be recognized that traditional equilibrium-based descriptions of NP–protein interactions, which encompass parameters like equilibrium binding affinity and corona composition, do not provide sufficient detail to predict NP behavior in vivo. This limitation arises because the open in vivo system is a nonequilibrium state characterized by constantly changing concentrations and dynamic regulation of biological processes. In light of these considerations, this review explores the kinetics and timescales of NP–protein interactions, discussing their relevance, fundamental concepts, measurement techniques, typical ranges of association and dissociation rate constants, and dynamics of protein corona formation and dissociation. The review concludes by outlining potential areas for further research and development in this field.