Biomedical Engineering Reference
In-Depth Information
ionic interactions taking place between the negative charges of the polyelectrolyte grafted on the
nanoparticle surface and patches of positive charges found on the proteins. It is believed that the
proteins can then adsorb as a multivalent counter-ion after the displacement of the monovalent
counter-ion found along the polyelectrolyte chains of the brush formed at the nanoparticle surface.
This effect can take place even at the most external sites of the nanoparticle corona as illustrated by
Figures 18.4a and b. The remarkable property of dextran sulfate to hinder the activation of the com-
plement system despite the adsorption of immunoglobulin and fibrinogen needs to be elucidated.
However, it can be assumed that the mechanism behind this effect is different from that depicted
with dextran-coated nanoparticles and based on a steric exclusion effect.
At this stage, we can identify that polysaccharide-coated nanoparticles can prevent the activation
of the complement system and control the adsorption of proteins by at least two mechanisms that
were summarized by Table 18.3.
More work is now needed to understand how proteins interact with nanoparticles and what
role the polysaccharide corona plays in this interaction. Nevertheless, the highly charged
nanoparticles appeared as potential drug carriers that were able to bypass recognition mecha-
nisms of the immune system followed by the activation of the complement cascade. Their capac-
ity to adsorb high-molecular weight proteins without triggering the activation of the complement
system is a new property. It can reasonably be assumed that they will show a different biodistri-
bution compared to that of the nanoparticles with a corona that selects small molecular weight
TABLE 18.3
Summary on Mechanisms Controlling Activation of the Complement System and
Adsorption of Proteins by Polysaccharide-Coated Nanoparticles and Major Type of
Proteins Adsorbed on Corresponding Nanoparticles
Composition of
the Nanoparticle
Corona = Brush
of Polysaccharide
Mechanism Behind
the Control of the
Activation of the
Complement System
Proposed Mechanism Behind the
Control of the Adsorption of Proteins
Type of Adsorbed Proteins
Adsorption on the hydrophobic core
surface of the nanoparticles after
diffusion through the polysaccharide
corona. Selection of proteins that can
adsorb arises by the characteristics of the
nanoparticle corona which function as a
molecular sieve and by the size and
shape of proteins which should fit with
that of the hydrophobic spaces available
on the nanoparticle core surface
Steric exclusion
Majority of low molecular
weight protein
(apolipoprotein A1 (Mw
28.08 kDa) and C2 (Mw
11.3 kDa))
Dextran > 60 kDa
Heparin
Adsorption of proteins as a multivalent
counterion by interactions of the charges
of the polysaccharides composing the
nanoparticle corona
Known activity
against complement
activation.
Interference with
factor H of the
complement cascade
Majority of high molecular
weight proteins.
Immunoglobulin,
fibrinogen
Dextran sulfate
Adsorption of proteins as a multivalent
counterion by interactions of the charges
of the polysaccharides composing the
nanoparticle corona
To elucidate
Majority of high molecular
weight proteins.
Immunoglobulin (Mw
150 kDa), fibrinogen
(Mw 340 kDa)
Chitosan
To elucidate
To elucidate
Unknown
