Stealth Nanoparticles Grafted with Dense Polymer BrushesDisplay Adsorption of Serum Protein Investigated by Isothermal TitrationCalorimetry

摘要

Core–shell nanoparticles receive much attention for their current and potential applications in life sciences. Commonly, a dense shell of hydrated polymer, a polymer brush, is grafted to improve colloidal stability of functional nanoparticles and to prevent protein adsorption, aggregation, cell recognition, and uptake. Until recently, it was widely assumed that a polymer brush shell indeed prevents strong association of proteins and that this leads to their superior “stealth” properties in vitro and in vivo. We show using T-dependent isothermal titration calorimetry on well-characterized monodisperse superparamagnetic iron oxide nanoparticles with controlled dense stealth polymer brush shells that “stealth” core–shell nanoparticles display significant attractive exothermic and enthalpic interactions with serum proteins, despite having excellent colloidal stability and negligible nonspecific cell uptake. This observation is at room temperature shown to depend only weakly on variation of iron oxide core diameter and type of grafted stealth polymer: poly(ethyleneglycol), poly(ethyl oxazoline), poly(isopropyl oxazoline), and poly(N-isopropyl acrylamide). Polymer brush shells with a criticalsolution temperature close to body temperature showed a strong temperaturedependence in their interactions with proteins with a significantincrease in protein binding energy with increased temperature. Thestoichiometry of interaction is estimated to be near 1:1 for PEGylatednanoparticles and up to 10:1 for larger thermoresponsive nanoparticles,whereas the average free energy of interaction is enthalpically drivenand comparable to a weak hydrogen bond.