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Review
. 2023 Mar 27;21(1):64.
doi: 10.1186/s12964-023-01089-1.

Protein corona and exosomes: new challenges and prospects

Morteza Heidarzadeh #  1 , Amir Zarebkohan #  2 , Reza Rahbarghazi  3   4 , Emel Sokullu  1   5
Affiliations
Review

Protein corona and exosomes: new challenges and prospects

Morteza Heidarzadeh et al. Cell Commun Signal. .

Abstract

Recent advances in extracellular vesicle (EVs) detection and isolation methods have led to the development of novel therapeutic modalities. Among different types of EVs, exosomes (Exos) can transfer different signaling biomolecules and exhibit several superior features compared to whole-cell-based therapies. Therapeutic factors are normally loaded into the Exo lumen or attached to their surface for improving the on-target delivery rate and regenerative outcomes. Despite these advantages, there are several limitations in the application of Exos in in vivo conditions. It was suggested that a set of proteins and other biological compounds are adsorbed around Exos in aqueous phases and constitute an external layer named protein corona (PC). Studies have shown that PC can affect the physicochemical properties of synthetic and natural nanoparticles (NPs) after introduction in biofluids. Likewise, PC is generated around EVs, especially Exos in in vivo conditions. This review article is a preliminary attempt to address the interfering effects of PC on Exo bioactivity and therapeutic effects. Video Abstract.

Keywords: Biodistribution; Exosomes; Physicochemical properties; Protein corona.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Formation of PC around Exos after exposure to biofluids. PC consists of external soft and internal hard layers
Fig. 2
Fig. 2
Exo hydrodynamic size is increased after PC information. Reduction of exosomal size after exposure to trypsin and especially proteinase K indicates a large number of soluble proteins attached to the Exo surface
Fig. 3
Fig. 3
PC formation on the surface of Exos inside in vivo conditions. Both hard and soft PC layers are generated around Exos as a result of non-specific interactions, and ligand-receptor affinity. The binding of different serum proteins on the exosomal surface can affect the hydrodynamic size, biodistribution, colloidal stability, and ligand-receptor interaction between Exos and acceptor cells. The formation of PC around Exos can also lead to the scavenging of these nanoparticles via the reticuloendothelial system. Meanwhile, the circulation time and delivery capacity of Exos are diminished as well. The binding of specific factors such as complement subsets increases the uptake of Exo by immune cells
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