Formation, biological consequences, and machine learning perspectives of protein corona on nanoparticles during digestion.

Nanoparticles (NPs) have been widely investigated for enhancing the stability, bioavailability, and functionality of bioactive compounds, as well as for broadening their application in biomedical and food-related fields. Upon exposure to biological environments, proteins spontaneously adsorb onto the surface of NPs and form dynamic protein corona (PC), which determine the interfacial properties and influence the biological behavior and fate of NPs. This review summarizes recent advances in the formation mechanisms, influencing factors, characterization strategies, and biological functions of PC associated with nanoparticle-based delivery systems. The effects of NPs physicochemical properties, environmental conditions, and nanoparticle-protein interactions on PC composition and evolution are discussed. Current approaches for characterizing PC structure, composition, and interfacial interactions are reviewed, highlighting the importance of integrating multiple analytical techniques for understanding PC formation and behavior. Furthermore, the impacts of PC on enzyme activity, cargo release, cellular interactions, and protein allergenicity are summarized. Recent applications of machine learning (ML) approaches in PC research are also discussed, focusing on their potential for integrating multidimensional data and facilitating the analysis of complex PC behaviors. A comprehensive understanding of PC formation and function will provide valuable insights into the rational design, performance evaluation, and safety assessment of nanoparticle-based delivery systems.