Abstract
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(ethylene glycol), poly(ethyl oxazoline), poly(isopropyl oxazoline), and poly(N-isopropyl acrylamide). Polymer brush shells with a critical solution temperature close to body temperature showed a strong temperature dependence in their interactions with proteins with a significant increase in protein binding energy with increased temperature. The stoichiometry of interaction is estimated to be near 1:1 for PEGylated nanoparticles and up to 10:1 for larger thermoresponsive nanoparticles, whereas the average free energy of interaction is enthalpically driven and comparable to a weak hydrogen bond.
Highlights
Core−shell nanoparticles receive ever increasing attention for their current and potential applications in life sciences.[1,2] Independent tailoring of the core and the shell is used to optimize particles to the many divergent functional demands on biomedical and biotechnological nanoparticles.[3,4] The core can provide functions such as imaging contrast, controlled drug storage and release as well as novel therapeutic functions.[5]
We have shown that serum proteins, albumin, adsorb to nanoparticles with cores smaller than 10 nm and stealth polymers grafted at spherical brush densities
The binding affinity of albumin was similar over a range of different stealth polymer brushes, but the number of proteins bound per particle seemed slightly lower for PEGylated particles than for particles grafted with poly(oxazoline) or poly(N-isopropyl acrylamid) (PNiPAm)
Summary
Core−shell nanoparticles receive ever increasing attention for their current and potential applications in life sciences.[1,2] Independent tailoring of the core and the shell is used to optimize particles to the many divergent functional demands on biomedical and biotechnological nanoparticles.[3,4] The core can provide functions such as imaging contrast, controlled drug storage and release as well as novel therapeutic functions.[5]. A seemingly successful strategy, the extent to which PEG brushes stabilize core−shell nanoparticles is not clear;[7] the requirements on polymer grafting density and molecular weight with respect to particle size and the extent of reduction in protein interaction are still open topics, the consensus is that achieving a very high and completely sterically blocking polymer concentration close to the core is required to benefit from brush repulsion.[8]
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