Due to their large surface area-to-volume ratio, nanoparticles (NPs) rapidly adsorb proteins on their surface upon contact with biological fluids, forming a "protein corona (PC)." The binding between NPs and proteins is primarily mediated by intermolecular forces such as hydrogen bonding, hydrophobic interactions, electrostatic interactions, and van der Waals forces. During this process, proteins with strong binding affinity can quickly form a so-called "hard PC" on the surface of NPs, surrounded by a "soft
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