proteins/peptides as well as other contaminants, resulting in low
ionization efficiency in mass spectrometry (MS) analysis [66]. To
their successful identification, the separation and enrichment of
proteins/peptides from complex mixtures are of great importance
[67]. Therefore, rapid, convenient, gentle, and efficient sample
preparation methods are necessary for biological analysis
[64]. The emergence of nanomaterials opened new horizons for
the fast, efficient, and convenient separation and enrichment of
biological macromolecules of the proteome.
In this way, the enrichment of peptides and proteins from
complex biological matrices using different nanomaterials before
MS analysis was developed without any further washing or separation procedures [68, 69].
In the last decade, an outburst in nanotechnology has revolutionized the field of medicine, opening intriguing new possibilities
for improving both diagnostic and therapeutic aspects [70]. Due to
the particular properties that appear when a material is reduced to
the nanoscale (1–100 nm), nanoparticles (NPs) are recognized as
promising agents for various biomedical applications [71].
Currently, it is known that the surfaces of NPs are rapidly
covered by different types of biomolecules when they contact
biological media [72–76]. This shell of active biomolecules forms
around NPs referred to as a protein corona (PC) [73]. The PC, also
known as the biomolecular corona, is mainly composed of proteins.
However, researchers also expect to find other biomolecules such as
lipids, metabolites, and sugars in future investigations [77, 78]. Protein “coronas” originally coined are complex structures, sometimes
20–30 nm thick, which consist of soft and hard layers, termed the
soft and hard corona. The soft corona (SC) is composed of proteins
involved in transient low-affinity interactions, while the hard
corona (HC) depends on more permanent high-affinity
interactions [79].
The phenomenon of PC formation is frequent among all
known NPs, except for a few with coatings such as zwitterionic
[80, 81] and has an important impact on the NP’s properties. PC
alters the physicochemical properties of the nanomaterials, including their size, charge, roughness, and aggregation state [82–
84]. Thus, the nanomaterials receive a new biological identity that
may be entirely different from their original pristine identity
[73, 85, 86]. What is clear to date is that the new identity given
by the PC is the main factor controlling biodistribution, therapeutic effect, and nanotoxicity of NPs in the body [85].
The protein composition and content in the corona depend on
several parameters, including (1) physicochemical properties of the
NPs (i.e., composition, size, shape, curvature, surface chemistry
and surface charge, hydrophobicity/hydrophilicity) [87–96];
(2) characteristics of biological media including protein and ionic
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