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Review
. 2018;25(35):4553-4586.
doi: 10.2174/0929867325666180601101859.

Coating Matters: Review on Colloidal Stability of Nanoparticles with Biocompatible Coatings in Biological Media, Living Cells and Organisms

Jonas Schubert  1   2 , Munish Chanana  3   4   5
Affiliations
Review

Coating Matters: Review on Colloidal Stability of Nanoparticles with Biocompatible Coatings in Biological Media, Living Cells and Organisms

Jonas Schubert et al. Curr Med Chem. 2018.

Abstract

Within the last two decades, the field of nanomedicine has not developed as successfully as has widely been hoped for. The main reason for this is the immense complexity of the biological systems, including the physico-chemical properties of the biological fluids as well as the biochemistry and the physiology of living systems. The nanoparticles' physicochemical properties are also highly important. These differ profoundly from those of freshly synthesized particles when applied in biological/living systems as recent research in this field reveals. The physico-chemical properties of nanoparticles are predefined by their structural and functional design (core and coating material) and are highly affected by their interaction with the environment (temperature, pH, salt, proteins, cells). Since the coating material is the first part of the particle to come in contact with the environment, it does not only provide biocompatibility, but also defines the behavior (e.g. colloidal stability) and the fate (degradation, excretion, accumulation) of nanoparticles in the living systems. Hence, the coating matters, particularly for a nanoparticle system for biomedical applications, which has to fulfill its task in the complex environment of biological fluids, cells and organisms. In this review, we evaluate the performance of different coating materials for nanoparticles concerning their ability to provide colloidal stability in biological media and living systems.

Keywords: Nanoparticles; biological media; biopolymers; coating materials; colloidal stability; polymeric coatings; protein corona..

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Figures

Fig. (1)
Fig. (1)
Schematic illustration of a typical approach for the synthesis of NPs and their surface modification prior to their biomedical applications. For the biomedical applications, the NP dispersions with their original coatings (small ligands, surfactants, polymers) are suspended either into biological media (e.g. buffers, cell culture media) or directly into the biofluids of the organism (e.g. blood), where the NPs eventually meet proteins. Depending on the surface chemistry and the coating material, the NP-protein interactions can differ and thus lead to different final properties of the NPs.
Fig. (2)
Fig. (2)
Ultraviolet–visible spectroscopy (UV/VIS) spectra of redispersed PEG–Au colloid in different dispersion media: (a) Dulbecco's Modified Eagle Medium (DMEM) containing 10% serum; (b) BSA; (c) HBSS and (d) NaCl (3 M). Reprinted with permission from ref. [140].
Fig. (3)
Fig. (3)
A) Quantification of human plasma proteins adsorbed at the NPs’ surface. The NPs consist of a polystyrene (PS) core and different shells (PEG or poly(ethyl ethylene phosphate)(PEEP)). B), Heat map of the most abundant proteins in the protein corona of PS-NH2, PS-PEG44, PS-PEG110, PS-PEEP49 and PS-PEEP92 determined by proteomic mass spectrometry. The indices represent the polymerization degree. C), Laser scanning microscopy images of RAW264.7 cells incubated with PS-NH2, PS-PEEP49, PS-PEEP92, PS-PEG44 and PS-PEG110 for 1 h in 100% human plasma(+Plasma) or DMEM without plasma(-Plasma). Figure reprinted with the permission of Nature Publishing Group [147].
Fig. (4)
Fig. (4)
Thermoresponsive NPs in biomedical studies. A) Schematic illustration of the phase transition of a thermoresponsive NP system. The size and surface properties of the NPs’ change below and above the transition temperature. B) Colloidal stability of Fe3O4@P(MEO2MA100-OEGMA10) NPs (POEGMA) at T below, equal to and above the LCST of the polymer coating. C) The transition temperature of the P(MEOMA-OEGMA)-coatings can be tuned by the molar ratio of the two monomers. The cellular uptake of such thermoresponsive NPs depends on the LCST of the polymer and the environmental temperature. As illustrated in D) Scheme of PLGA-b-(PEGMEMA-co-PPGMA) NP at temperatures below and above the LCST. Above the LCST the particles are more hydrophobic and therefore the uptake of cells is higher E)This was proven by confocal micrographs of MCF-7 cells treated with R6G-loaded NPs at 37 °C and 40 °C, showing enhanced signal at 40°C. F) The NPs retain their thermoresponsive behavior inside the cells and agglomerate and disagglomerate reversibly inside the cells, as shown by rhodamine labelled Fe3O4@P(MEO2MA90-OEGMA10) NPs. Reprinted with permission form ref. [68, 179, 180].
Fig. (5)
Fig. (5)
Synthesis and physicochemical properties of protein-coated Au NPs and Au NRs. A) Schematic illustration of the synthesis of protein-coated NPs in a ligand exchange process. B) Transmission electron microscopy (TEM) image of 15 nm spherical Au NPs coated with the 2 nm protein coating (insulin). C) The localized surface plasmon resonance (LSPR) band indicates no aggregation during the coating process, revealing a successful coating. D) By taking the environmental parameters into account, various types of proteins and enzymes can be coated onto Au NPs. The photograph shows dispersions of Au NPs coated with proteins of different pI (increasing from left to right). TEM images (E) and LSPR band of Au NRs of different aspect ratios. Similar to the Au NPs, protein-coated Au NRs are also highly stable in various buffers and cell culture media (G) and in serum containing media (H). They can be freeze dried and are stable at high particle concentrations (H). Reprinted with permission from ref. [88, 142, 146].
Fig. (6)
Fig. (6)
A) Stability of Au@protein NPs (Au@Ovalbumin- 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pro-pionic acid (Au@Ova-Bodipy, Au@Ova-DQ) under lysosomal conditions, i.e. under acidic conditions (pH 4.7) in the presence of proteases. The NPs aggregate because of their pH-sensitive character. After incubation for 18 h at 37°C (central photograph), the pH of the dispersions was raised to the physiological pH of 7.4 (right photograph). B) UV/VIS spectra of the protease-containing mixtures in (A). C) Time-dependent fluorescence release of Au@Ova-DQ in 3T3 fibroblasts upon enzymatic digestion of the fluorescently labelled protein coating. Confocal laser scanning microscopy (CLSM) images of 3T3 fibroblasts incubated with the Au@Ova-DQ NPs. The images were recorded at the same position at different times, as indicated. The images are an overlay of the fluorescence (green) and transmission channel. Scale bars: 20 m. D) Schematic illustration of the behavior of protein-coated NPs inside cells and cellular compartments and the prediction of their colloidal stability in the various biological environments. Reprinted with permission from Ref. [143]. (The color version of the figure is available in the electronic copy of the article).
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