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A health concern regarding the protein corona, aggregation and disaggregation - PubMed

Review

A health concern regarding the protein corona, aggregation and disaggregation

Mojtaba Falahati et al. Biochim Biophys Acta Gen Subj. 2019 May.

Abstract

Nanoparticle (NP)-protein complexes exhibit the "correct identity" of NP in biological media. Therefore, protein-NP interactions should be closely explored to understand and modulate the nature of NPs in medical implementations. This review focuses mainly on the physicochemical parameters such as dimension, surface chemistry, morphology of NPs, and influence of pH on the formation of protein corona and conformational changes of adsorbed proteins by different kinds of techniques. Also, the impact of protein corona on the colloidal stability of NPs is discussed. Uncontrolled protein attachment on NPs may bring unwanted impacts such as protein denaturation and aggregation. In contrast, controlled protein adsorption by optimal concentration, size, pH, and surface modification of NPs may result in potential implementation of NPs as therapeutic agents especially for disaggregation of amyloid fibrils. Also, the effect of NPs-protein corona on reducing the cytotoxicity and clinical implications such as drug delivery, cancer therapy, imaging and diagnosis will be discussed. Validated correlative physicochemical parameters for NP-protein corona formation frequently derived from protein corona fingerprints of NPs which are more valid than the parameters obtained only on the base of NP features. This review may provide useful information regarding the potency as well as the adverse effects of NPs to predict their behavior in vivo.

Keywords: Aggregation; Amyloid disaggregation; Clinical application; Colloidal stability; Cytotoxicity; Protein corona.

Copyright © 2019 Elsevier B.V. All rights reserved.

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Figures

Fig. 1
Fig. 1

Protein corona structure mostly depend on the physicochemical properties of NPs such as size, shape, surface functional groups, and pH of medium.

Fig. 2
Fig. 2

Adsorption of protein on larger NPs results in larger conformational changes compared to interaction with smaller NPs. Hence the size can influence the kind of interactions between NP and proteins.

Fig. 3
Fig. 3

The pH-dependent denaturation of BSA after interaction with AuNPs. Different pH of medium induces different charge distribution on the protein surfaces and subsequent interactions and denaturation.

Fig. 4
Fig. 4

The surface chemistry of AuNPs mediates the degree of NP-triggered conformational changes of Cyt C. When AuNPs having positive, negative and neutral ligands adjacent to interacted with cytochrome C, the structure of cytochrome C changes with a shift in the ions of NPs. Protein maintains its structure with neutral ligands, but changes in the presence of other ions. Reprinted with permission from reference [51].

Fig. 5
Fig. 5

Depending on the surface properties of NPs, proteins do not adsorb on NPs. AuNPs incorporated with a double mixture of hydrophobic and hydrophilic thiolated ligand molecules have been shown to form a ligand shell with stripe-like domains of alternating hydrophobic/hydrophilic combination. These stripe-like domains have a characteristic thickness, leading to surface heterogeneities at similar scales as those found on proteins. Reprinted with permission from reference [52].

Fig. 6
Fig. 6

Different interactions with Au NPs and corresponding structural changes of BSA dependent on the variations in NP morphology.

Fig. 7
Fig. 7

a) Hydrodynamic radius DHversus time for 7 nm coated and uncoated iron oxide NPs in the cell culture medium supplemented with 10% heat-inactivated fetal bovine serum (FBS). For uncoated particles as well as for cliavist® NP aggregation occurs. Particles coated with polymers (e.g. poly(acrylic acid) and phosphonic acid PEG copolymers) remain disperse for several months and devoid of protein corona [64]. b) Same as in a) for 7 nm cerium oxide NPs (CeO2) coated with citrate and poly(acrylic acid) [84]. c) TEM images of lymphoblastoid cells treated with Cit–γ-Fe2O3 NPs for 24 h at [Fe] = 10 mM; c1) and c2) demonstrate NPs enclosed in an endosome and clusters, respectively. Bars are 2 μm in c) and 300 nm in c1–c2) [59]. d) Same as in c) for lymphoblastoid cells incubated with PAA2K–γ-Fe2O3NPs for 24 h at [Fe] = 10 mM; b1) exhibits NPs enclosed in 200 nm endosomes. Bars in d) are 2 μm and 300 nm in d1) [59].

Fig. 8
Fig. 8

Schematic representation of cell-NP interactions. Uncoated NPs aggregate in the presence of serum protein and are either internalized into endosomes in large quantities or sticking at the membrane. Polymer coated NPs in contrast are much less internalized and are located intracellularly in endosomes [59,84,211].

Fig. 9
Fig. 9

AuNPs initiate amyloid nucleation, causing the formation of protein aggregation without embedded NPs. Reprinted with permission from reference [90].

Fig. 10
Fig. 10

NPs accelerated amyloid nucleation of stable protein

Fig. 11
Fig. 11

Protein adsorption on the NP surface results in small amounts of free protein in the solution. Thus, the binding process causes retardation of amyloid nucleation phase. Reprinted with permission from reference [99].

Fig. 12
Fig. 12

Nano-EGCG protects neuronal cells from the adverse effects of extracellular polyglutamine (polyQ) aggregates or protein aggregates by inhibiting their amyloid induction. Reprinted with permission from reference [105].

Fig. 13
Fig. 13

Trehalose-modified AuNPs can play an inhibitory impact on intracellular polyglutamine-containing mutant protein amyloid elongation. Reprinted with permission from reference [106].

Fig. 14
Fig. 14

Sugar-modified NP inhibits the induction of protein amyloid and decrease the adverse effects of aggregated proteins on the cells. Reprinted with permission from reference [107].

Fig. 15
Fig. 15

Adsorption of HSA on dihydrolipoic acid-coated quantum dots (DHLA-QDs) affected adhesion velocity to the cell membrane and infiltrate outcome for HeLa cells. (A) Adsorption of different HSA proteins onto DHLA-QDs. (B) Cells were treated with QDs in the absence or presence of different HSA proteins. (C) Quantification of NP uptake. Reprinted with permission from reference [122].

Fig. 16
Fig. 16

The cytotoxicity of graphene oxide was markedly reduced at cell culture medium. Reprinted with permission from reference [125].

Fig. 17
Fig. 17

Possible uptake process and mechanisms of cytotoxicity induced by NPs and mitigated toxicity by corona protein in cells based on the metadata from several studies.

Fig. 18
Fig. 18

Schematic illustration of NPs bio-diffusion with varying coatings.

Fig. 19
Fig. 19

Schematic representation of NPs construction and drug transfer with irradiation therapy in target cells.

Fig. 20
Fig. 20

(a) Schematic illustration of the development of HSA-IO NPs. (b) Illustrative in vivo NIRF images of mouse inoculated with HSA-IONPs. Images were acquired 1 h, 4 h and 18 h post injection. (c) In vivo PET imaging outcomes of mouse inoculated with HSA-IONPs. Images were obtained 1 h, 4 h and 18 h post injection. (d) MRI images obtained before and 18 h post inoculation. Reprinted with permission from reference [157].

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