Multivariate Analysis of Protein–Nanoparticle Binding Data Reveals a Selective Effect of Nanoparticle Material on the Formation of Soft Corona

When nanoparticles are introduced into the bloodstream, plasma proteins accumulate at their surface, forming a protein corona. This corona affects the properties of intravenously administered nanomedicines. The firmly bound layer of plasma proteins in direct contact with the nanomaterial is called the “hard corona”. There is also a “soft corona” of loosely associated proteins. While the hard corona has been extensively studied, the soft corona is less understood due to its inaccessibility to analytical techniques. Our study used dynamic light scattering to determine the dissociation constant and thickness of the protein corona formed in solutions of silica or gold nanoparticles mixed with serum albumin, transferrin or prothrombin. Multivariate analysis showed that the nanoparticle material had a greater impact on binding properties than the protein type. Serum albumin had a distinct binding pattern compared to the other proteins tested. This pilot study provides a blueprint for future investigations into the complexity of the soft protein corona, which is key to developing nanomedicines.