Biomedical Engineering Reference
In-Depth Information
Protein corona is complex and there is no one “universal” plasma protein corona
for all nanomaterials and that the relative densities of the adsorbed proteins do not
correlate with their relative abundances in plasma. Thus, the composition of the
protein corona is unique to each nanomaterial and depends on many parameters.
2.1 Structure and Composition of Corona
The majority of adsorbed biomolecules on the surface of nanoparticles in blood
plasma are proteins, and recently some minor traces of lipids have also been
reported. The adsorption of proteins on the surface of nanoparticle is governed by
protein-nanoparticle binding affinities as well as protein-protein interactions.
Proteins that adsorb with high affinity form what is known as the “hard” corona,
consisting of tightly bound proteins that do not readily desorb, and proteins that
adsorb with low affinity form the “soft” corona, consisting of loosely bound
proteins (Fig.
2.1a
). Soft and hard corona can also be defined based on their
exchange times. Hard corona usually shows much larger exchange times in the
order of several hours [
1
].
A hypothesis is that the hard corona proteins interact directly with the
nanomaterial surface, while the soft corona proteins interact with the hard corona
via weak protein-protein interactions [
2
]. There is a general observation that even
at low plasma concentrations, there is a complete surface coverage of corona layer
[
1
]. However, the adsorbed corona does not completely mask the surface of
nanoparticle or its functional groups. In a study on dextran-coated superpara-
magnetic iron oxide nanoparticles (SPIONs), the incubation of SPIONs in plasma
and formation of the protein corona did not significantly changed the circulation
lifetime [
3
].
The thickness of protein corona can be a factor of many parameters such as
protein concentration, particle size, and surface properties of particle. Most plasma
proteins present a hydrodynamic diameter of about 3-15 nm; thus, the coronas on
these nanoparticles are too thick to be composed of only a single layer of adsorbed
protein and are composed of multiple layers. A model for the protein corona has
been proposed by Simberg et al. [
3
]; it consists of “primary binders” that recognize
the nanomaterial surface directly and “secondary binders” that associate with the
primary binders via protein-protein interactions. Such a multilayered structure is
significant for the physiological response as the secondary binders may alter the
activity of the primary binders or “mask” them, preventing their interaction with the
surrounding environment.
In a recent review, Walkey and Chan [
2
] summarized a subset of 125 plasma
proteins, called adsorbome, that were identified in protein corona of at least one
nanomaterial. This list will probably expand due to further studies in the future.
Results compiled over many studies since about 20 years ago showed that a
“typical” plasma protein corona consists of approximately 2-6 proteins adsorbed
with high abundance and many more adsorbed with low abundance. Only a small
