Debugging the dynamics of protein corona: Formation, composition, challenges, and applications at the nano-bio interface

The intricate interplay between nanomaterials and the biological molecules has garnered considerable interest in understanding the dynamics of protein corona formation at the nano-bio interface. This review provides an in-depth exploration of protein-nanoparticle interactions, elucidating their structural dynamics and thermodynamics at the nano-Bio interface and further on emphasizing its formation, composition, challenges, and applications in the biomedical and nanotechnological domains, such as drug delivery, theranostics, and the translational medicine. We delve the nuanced mechanisms governing protein corona formation on nanoparticle surfaces, highlighting the influence of nanoparticle and biological factors, and review the impact of corona formation on the biological identity and functionality of nanoparticles. Notably, emerging applications of artificial intelligence and machine learning have begun to revolutionize this field, enabling accurate prediction of corona composition and related biological outcomes. These tools not only enhance efficiency over traditional experimental methods but also help decode complex protein-nanoparticle interaction patterns, offering new insights into corona-driven cellular responses and disease diagnostics. Additionally, it discusses recent advancements in the field of protein corona, particularly in translational nanomedicine and associated applications entailing current and future strategies which are aimed at mitigating the adverse effects of protein-nanoparticle interactions at the biological interface, for tailoring the protein coronas by engineering of the nanomaterials. This comprehensive assessment from chemical, technological, and biological aspects serves as a guiding beacon for the development of future nanomedicine, enabling the more effective emulation of the biological milieu and the design of protein-NP systems for enhanced biomedical applications.