Polymer Brush-Grafted Nanoparticles Preferentially Interact with Opsonins and Albumin

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.

Thermoresponsive Nanoparticles with Cyclic-Polymer-Grafted Shells Are More Stable than with Linear-Polymer-Grafted Shells: Effect of Polymer Topology, Molecular Weight, and Core Size

“…Thus, it was recently shown that cyclic polymer brush shells on small iron oxide nanoparticles provide qualitatively and quantitatively improved colloidal stability and protection against the adsorption of human serum albumin compared to equivalent linear polymer brush shells. 32 , 37 , 38 …”

“…Thus, it was recently shown that cyclic polymer brush shells on small iron oxide nanoparticles provide qualitatively and quantitatively improved colloidal stability and protection against the adsorption of human serum albumin compared to equivalent linear polymer brush shells. 32,37,38 Cyclic polymers have previously been investigated for their thermal stability as micelles. Tezuka and co-workers described higher thermal stability of cyclic block copolymers compared to chemically identical linear ABA triblock copolymers.…”

“…Polymers, e.g., biopolymer such as proteins, can penetrate dynamic defects in less dense linear brush shells and allow strong adsorption within the shell. Thus, it was recently shown that cyclic polymer brush shells on small iron oxide nanoparticles provide qualitatively and quantitatively improved colloidal stability and protection against the adsorption of human serum albumin compared to equivalent linear polymer brush shells. ,, …”

Polymer brush-based nanostructures: from surface self-assembly to surface co-assembly

“…32 Responsive polymer brushes have been widely used in antibacterial, 33 antifouling, 34,35 surface wetting, 36,37 and biomedical materials. [38][39][40] Therefore, the fabrication of the polymer brushes is widely recognized as one of the most powerful tools to control the surface properties. 41…”

Polymer-tethered glycosylated gold nanoparticles recruit sialylated glycoproteins into their protein corona, leading to off-target lectin binding

“… 29 The challenge of preventing this corona is highlighted by even very dense polymer brushes, which resist certain proteins (lyzosyme/transferrin) but selectively captured albumin and immunoglobulins. 30 The protein corona is hence of crucial consideration for any material, with cells ‘seeing’ this, rather than the underpinning nanoparticle itself, meaning the hard corona composition defines any interactions. 31 These proteins can be described as the hard (irreversibly bound) and soft (reversibly bound) corona.…”