Nanotechnology has brought countless novel applications regarding therapeutic, diagnostic, and sensing innovations. In particular, nanoparticle engineering enables the synthesis of nanocrystals with customized physical, chemical, and biological activities, which are generally well validated in vitro. However, when nanoparticles are tested in vivo they often show a disappointing loss of efficacy or increase of toxicity. These phenomena are related to the interaction of the nanoparticle surface with proteins, lipids, and ions present in the blood stream. Herein, we assess the physicochemical properties of an array of iron oxide nanoparticles coated with 15 different biocompatible materials dispersed in physiological aqueous media and human blood plasma. Our findings establish valid criteria for the prediction of the colloidal stability of nanoparticles dispersed in physiological aqueous media and human blood plasma. The criteria are based on the hydrophilicity and the net surface charge of the pristine nanoparticle coating in water dispersion. Hence, the methodology to select the most adequate nanoparticle coating for in vivo studies will be improved.

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