The protein corona at the nano-bio interface: the need for standardized methodology and opportunities for neurodegenerative disease intervention.

The "biological identity" of a nanoparticle is determined not only by its surface but by the complex protein corona (PC) it forms when entering a biological system. There have been significant advances in nanoparticle (NP) design that overcome various barriers, however, the protein corona remains a major challenge in the field of nanotechnology. Despite the use of various analytical techniques and a wide range of experimental conditions in protein corona research, there is a critical need for standardized, high-resolution methods to achieve the most accurate and comprehensive characterization of the protein corona. Improving technical transparency and reproducibility will help develop a more predictable framework for nanomedicine. This review first highlights how the physicochemical properties of NPs and the biological environment influence PC formation. Next, we emphasize the urgent need for standardized methodologies and techniques for their characterization to enhance understanding of protein corona formation and to increase reproducibility in nanomedicine studies. Additionally, to explore the untapped potential of NPs in either accelerating or inhibiting the pathological hallmarks of neurodegenerative diseases, this review summarizes how NPs modulate protein aggregation and fibril formation, and discusses the impact of PC on the process of amyloid fibrillation.