Isothermal titration calorimetry as a complementary method for investigating nanoparticle–protein interactions

Isothermal titration calorimetry (ITC) is a complementary technique that can be used for investigations of protein adsorption on nanomaterials, as it quantifies the thermodynamic parameters of intermolecular interactions in situ. As soon as nanomaterials enter biological media, a corona of proteins forms around the nanomaterials, which influences the surface properties and therefore the behavior of nanomaterials tremendously. ITC enhances our understanding of nanoparticle-protein interactions, as it provides information on binding affinity (in form of association constant Ka), interaction mechanism (in form of binding enthalpy ΔH, binding entropy ΔS and Gibbs free energy ΔG) and binding stoichiometry n. Therefore, as a complementary method, ITC enhances our mechanistic understanding of the protein corona. In this minireview, the information obtained from a multitude of ITC studies regarding different nanomaterials and proteins are gathered and relations between nanomaterials' properties and their resulting interactions undergone with proteins are deduced. Nanomaterials formed of a hydrophilic material without strongly charged surface and steric stabilization experience the weakest interactions with proteins. As a result, such nanomaterials undergo the least unspecific protein-interactions and are most promising for allowing an engineering of the protein corona.