Polymer Brush-Grafted Nanoparticles Preferentially Interact with Opsonins and Albumin.

Nikolaus Simon Leitner,Martina Schroffenegger,Erik Reimhult

doi:10.1021/acsabm.0c01355

Nikolaus Simon Leitner, Martina Schroffenegger + Show 1 more

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https://doi.org/10.1021/acsabm.0c01355

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Abstract

Nanoparticles find increasing applications in life science and biomedicine. The fate of nanoparticles in a biological system is determined by their protein corona, as remodeling of their surface properties through protein adsorption triggers specific recognition such as cell uptake and immune system clearance and nonspecific processes such as aggregation and precipitation. The corona is a result of nanoparticle–protein and protein–protein interactions and is influenced by particle design. The state-of-the-art design of biomedical nanoparticles is the core–shell structure exemplified by superparamagnetic iron oxide nanoparticles (SPIONs) grafted with dense, well-hydrated polymer shells used for biomedical magnetic imaging and therapy. Densely grafted polymer chains form a polymer brush, yielding a highly repulsive barrier to the formation of a protein corona via nonspecific particle–protein interactions. However, recent studies showed that the abundant blood serum protein albumin interacts with dense polymer brush-grafted SPIONs. Herein, we use isothermal titration calorimetry to characterize the nonspecific interactions between human serum albumin, human serum immunoglobulin G, human transferrin, and hen egg lysozyme with monodisperse poly(2-alkyl-2-oxazoline)-grafted SPIONs with different grafting densities and core sizes. These particles show similar protein interactions despite their different “stealth” capabilities in cell culture. The SPIONs resist attractive interactions with lysozymes and transferrins, but they both show a significant exothermic enthalpic and low exothermic entropic interaction with low stoichiometry for albumin and immunoglobulin G. Our results highlight that protein size, flexibility, and charge are important to predict protein corona formation on polymer brush-stabilized nanoparticles.

Highlights

Core−shell nanoparticles are an exciting tool for many current and future biomedical applications.[1−4] They are biphasic composite materials consisting of an inner core and an outer shell with different material properties
In follow-up work, we demonstrated that human serum albumin (HSA) adsorption is completely suppressed on superparamagnetic iron oxide nanoparticles (SPIONs) with a brush shell architecture using cyclic topology compared to the traditional linear brush-stabilized particles ubiquitously in use.[44,45]
The exceptions were (1-cyano-2-ethoxy-2oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (COMU) that was purchased from Carl Roth, 2ethyl-2-oxazoline that was dried over CaH2 before use, and methyl-ptoluenesulfonate that was distilled before use. (4-(2-Hydroxyethyl)-1piperazineethanesulfonic acid) (HEPES), NaCl, KCl, recombinant human serum albumin, hen egg lysozyme, human transferrin, and human immunoglobulin G (IgG) from serum were purchased from Sigma-Aldrich

Summary

Introduction

Core−shell nanoparticles are an exciting tool for many current and future biomedical applications.[1−4] They are biphasic composite materials consisting of an inner core and an outer shell with different material properties. For example, iron oxide, can be used as a contrast agent for bioimaging or as a signal-transducing element for in vivo biosensing, while a polymeric, porous, or vesicle core can act as a storage and release vessel for drug delivery.[3,5] The physicochemical properties of a nanoparticle determine their usefulness in these respects and decide their biological fate.[6,7] These properties are highly dependent on the shape, size, and type of the material and, extremely sensitive to aggregation with other particles or macromolecules in the environment.[6,8]. Proteins with low affinity form a loosely bound “soft protein corona” in equilibrium with the bulk.[6,11,14−16] The “hard corona” is easy to analyze, while only little is known about the amount and identity of proteins in the “soft corona” because of the low affinity and weak binding of the involved proteins.[17]

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