Biomedical Engineering Reference
In-Depth Information
C3
C3
R1
R3
C3
C3
A1, A2
R2
FIGURE 18.5
(
See color insert.
) A scheme illustrating the interactions of proteins with a series of nanopar-
ticles having corona of dextran with different characteristics. The dark spot included in C3 indicates that the
component C3 of the complement system is activated. Albumin adsorbed on the surface of the nanoparticle
core appears as a dark triangle.
and the grafting density. A triage between proteins of high and low molecular weights applied at
two levels. As explained above, the type of proteins that can adsorb onto the nanoparticle's surface
depends on their size and the hydrophobic areas available on the nanoparticle core. It also depends
on the characteristics of the corona, which functions as a molecular sieve, while proteins diffuse
across.
Proteins whose size and geometry does not allow them to diffuse through the mesh of the poly-
saccharide layer that forms the corona are excluded from and are not able to reach the surface of the
nanoparticle's hydrophobic core (Figure 18.6).
As it was found with PEG-coated nanomaterials, the density of the dextran chain stranded on the
surface of nanoparticles, their molecular weight, and their conformation are factors that contribute
to the selection of the amount and type of proteins that adsorb onto the nanoparticle's surface. These
factors also control the activation of protein C3 of the complement system, which plays a central role
in the activation of the immune system's complement cascade (Nilsson et al., 2007). A clear correla-
tion was highlighted between the levels of activation produced by the nanoparticles and the mesh
size characteristics of the polysaccharide brush composing their corona (Figure 18.7a). Considering
this correlation, it clearly appeared that the steric exclusion of protein C3 from the nanoparticle
corona could prevent the activation of the complement system. The correlation between the prob-
ability of insertion of protein C3 in the dextran corona and the level of activation measured was not
as good (Figure 18.7b). This was interpreted by the fact that the activation of protein C3 may be
triggered by a layer of already-adsorbed proteins which have changed conformation during adsorp-
tion onto the nanoparticle core surface, and that may be accessible to protein C3 from the external
part of the nanoparticles.
As discussed above, the density, conformation, and concentration of dextran chains on the
nanoparticle corona are factors controlling the adsorption of proteins and activation of complement.
Activation of protein C3 of the complement system was also controlled by the molecular weight of
the dextran chains in the brush (Figure 18.8).
Nanoparticles that activated protein C3 had a brush of dextran chains with a molecular weight
lower than 60 kDa. With a brush formed by dextran of higher molecular weight, the nanoparticles
hampered the activation of protein C3, which is mandatory in escaping the immune system in the
vascular compartment. This result was not expected from the other characteristics of the nanoparti-
cle corona because protein C3 was believed to be too large to diffuse through the dextran corona and
reach the surface of the nanoparticle core to be activated. As illustrated in Figure 18.6 for nanopar-
ticle R3, the activation of protein C3 could be triggered by a layer of adsorbed proteins protruding
