Toward the Specificity of Bare Nanomaterial Surfaces for Protein Corona Formation

Abstract

Aiming at creating smart nanomaterials for biomedical applications, nanotechnology aspires to develop a new generation of nanomaterials with the ability to recognize different biological components in a complex environment. It is common opinion that nanomaterials must be coated with organic or inorganic layers as a mandatory prerequisite for applications in biological systems. Thus, it is the nanomaterial surface coating that predominantly controls the nanomaterial fate in the biological environment. In the last decades, interdisciplinary studies involving not only life sciences, but all branches of scientific research, provided hints for obtaining uncoated inorganic materials able to interact with biological systems with high complexity and selectivity. Herein, the fragmentary literature on the interactions between bare abiotic materials and biological components is reviewed. Moreover, the most relevant examples of selective binding and the conceptualization of the general principles behind recognition mechanisms were provided. Nanoparticle features, such as crystalline facets, density and distribution of surface chemical groups, and surface roughness and topography were encompassed for deepening the comprehension of the general concept of recognition patterns.

Keywords: biomolecules; nanoparticles; protein corona; surface recognition; uncoated nanomaterials.

Figure 1

In the schematic representation, upon exposure to a biological milieu, most of the nanoparticles reported in the literature (yellow) are subjected to the unspecific binding of proteins (red). On the contrary, nanoparticles displaying binding selectivity (grey) lead to the formation of a shell composed of specific proteins (blue) promoting cell internalization. This biological envelope makes the difference between nanoparticles being internalized or being cleared by the immune system. Arrows represent the Vroman effect.

Figure 2

Apolipoprotein A1 recognition of nanoparticle surface (left) and electron microscopy images of biological samples showing nanoparticle uptake in Zebrafish (right): (A) photomicrograph of a liver parenchyma cross-section showing the organization of hepatocyte cells (hematoxylin and eosin staining); (B) transmission electron microscopy image of hepatocyte cells surrounding a capillary; (C) high magnification of the region shown in (B) revealing nanoparticles (arrows) inside the capillary; (D) transmission electron microscopy image of nanoparticles in the space between the follicular epithelium and zona radiata of the zebrafish ovary (reproduced with permission from [70]).

Figure 3

Circular dichroism (CD) and EDS chemical mapping on HR-TEM micrographs of arsenic (As(III) and As(V)) coated iron oxide nanoparticles. Panel (A): CD spectra of unmodified nanoparticles (black continuous line), As(III) or As(V) modified nanoparticles (red and blue continuous lines, respectively), and As(III), As(V) as controls (red and blue dashed lines, respectively). Panel (B) and (C): mapping of nanoparticle surface sites displaying chiroptical activity: the distribution of As(III) (panel (A)) and As(V) (panel (C)) oxyacids from EDS chemical mapping on HR-TEM micrographs. Segmented white lines represent the (220) planes of iron oxide crystalline lattice (reproduced with permission from [93]).

Figure 4

Three dimensional computational models of proteins displaying selectivity toward iron oxide nanoparticles (A,B,E,F) and proteins with no affinity for iron oxide nanoparticles (C,D,G,H). Patterns of carboxylic groups can be visualized on specific sides of the macromolecules. (A,B) = xanthine oxidase (XO); (C,D) = bovine serum albumin (BSA); (E,F) = aminoaldehyde dehydrogenase 1 from tomato (SlAMADH1, from Solanum lycopersicum); (G,H) = bovine serum amine oxidase (BSAO) (reproduced with permission from [117]).

Figure 5

Surface mapping emerges as the key to understanding the high level of complexity and specificity that can be obtained in the interaction between proteins and bare inorganic surfaces.