Protein–Nanoparticle Interaction: Corona Formation and Conformational Changes in Proteins on Nanoparticles

Nanoparticles (NPs) are highly potent tools for the diagnosis of diseases and specific delivery of therapeutic agents. Their development and application are scientifically and industrially important. The engineering of NPs and the modulation of their in vivo behavior have been extensively studied, and significant achievements have been made in the past decades. However, in vivo applications of NPs are often limited by several difficulties, including inflammatory responses and cellular toxicity, unexpected distribution and clearance from the body, and insufficient delivery to a specific target. These unfavorable phenomena may largely be related to the in vivo protein-NP interaction, termed "protein corona." The layer of adsorbed proteins on the surface of NPs affects the biological behavior of NPs and changes their functionality, occasionally resulting in loss-of-function or gain-of-function. The formation of a protein corona is an intricate process involving complex kinetics and dynamics between the two interacting entities. Structural changes in corona proteins have been reported in many cases after their adsorption on the surfaces of NPs that strongly influence the functions of NPs. Thus, understanding of the conformational changes and unfolding process of proteins is very important to accelerate the biomedical applications of NPs. Here, we describe several protein corona characteristics and specifically focus on the conformational fluctuations in corona proteins induced by NPs.