concentrations [97], protein source (e.g., fetal bovine serum,
serum, or plasma) [98–100], choice of anticoagulant [101], flow
status (dynamic vs. static) [100], and temperature [102]; and
(3) incubation time [83, 103].
On the other hand, early detection and diagnosis of cancer are
critical for effective treatment and reduced mortality. Regardless of
recent advances in molecular diagnostics, noninvasive screening
tests for early-stage cancer detection are almost nonexistent for
most cancer types. The very limited few existing screening tests,
such as prostate-specific antigen (PSA) test for prostate cancer,
colonoscopy for colorectal cancer, mammogram for breast cancer,
and low-dose computerized tomography (LDCT) scan for lung
cancer, either suffer the low specificity and low sensitivity or involve
rather invasive and labor-intensive medical procedures, or are too
costly to be used for screening purpose [104]. There is a continuing
and pressing medical need to develop noninvasive tests for earlystage cancer detection and screening.
Ideally, proteomics, as a large-scale study of proteins, could be
employed in diagnostics by individuating specific proteome variations correlated with diseases. Nevertheless, the complexity of the
proteome does not allow a straightforward interpretation of its
changes.
It is well known that each type of disease has significant effects
on the concentration/confirmation of plasma/serum proteins.
Furthermore, the genetic background, lifestyle, posttranslational
modification, and geographical origin play an important role in
the changes in plasma/serum proteins in healthy individuals
[105]. Moreover, the structure/concentration of some significant
proteins present in human plasma/serum can be substantially
altered by medical conditions and diseases (e.g., cancer, obesity,
diabetes, hemodialysis, rheumatism, hypercholesterolemia, fauvism, hemophilia, hypofibrinogenemia, smoking, and pregnancy)
[98]. Importantly, due to its high concentration in the human
plasma/serum, albumin also plays a key role in the formation of
the PC [90]. Firstly, albumin tends to be adsorbed on the NP
surface after a short incubation, and then, it is replaced by other
proteins with higher affinities [91]. Thus, changed/modified
plasma/serum proteins can be considered as potential prognostic
or diagnostic biomarkers for predicting/treating specific disorders.
Notably, the composition of the protein corona varies among
healthy individuals, as well as among patients with various diseases/
medical conditions. Thus, the same NPs may have different protein
coronas in different individuals. These alterations are often small
and challenging to be detected by conventional blood analyses. On
the other side, the protein corona can act as a “nano-concentrator”
[106] of those serum proteins with affinity for the NP surface.
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