The Protein Corona Paradox: Challenges in Achieving True Biomimetics in Nanomedicines.

Abstract

Nanoparticles introduced into biological environments rapidly acquire a coating of biomolecules, forming a biocorona that dictates their biological fate. Among these biomolecules, proteins play a key role, but their interaction with nanoparticles during the adsorption process often leads to unfolding and functional loss. Evidence suggests that protein denaturation within the biocorona alters cellular recognition, signaling pathways, and immune responses, with significant implications for nanomedicine and nanotoxicology. This review explores the dynamic nature of the protein corona, emphasizing the influence of the local biological milieu on its stability. We synthesize findings from studies examining the physicochemical properties of nanoparticles-such as surface charge, hydrophobicity, and curvature-that contribute to protein structural perturbations. Understanding the factors governing protein stability on nanoparticle surfaces is essential for designing nanomaterials with improved targeting, biocompatibility, and controlled biological interactions. This review underscores the importance of preserving protein conformational integrity in the development of nanoparticles for biomedical applications.