Biomedical Engineering Reference
In-Depth Information
Activation
of C3
A1
A2
R1
R3
+
+
-
+
40
30
20
10
0
Low Mw
proteins
Immuno
globulin
Fibrinogen
Low Mw proteins
Apolipoproteins A1, A2, and C2
(Mw 28, 17, and 11 kDa)
Transthyretin (Mw 14 kDa)
Albumin (Mw 66 kDa)
Apolipoprotein J (Mw 70 kDa)
Transferrin (Mw 76.5 kDa)
High Mw proteins
lg (Mw 150 kDa)
Fibrinogen (Mw 340 kDa)
FIGURE 18.8 Protein adsorption on different dextran-coated nanoparticles and corresponding status of the
activation of protein C3 of the complement system. The circles at the bottom represent the balance between
proteins of high molecular weight (>100 kDa) (dark gray and black) and low molecular weight (<100 kDa)
(light gray) that were found adsorbed at the nanoparticle surface after incubation in plasma. For proteins of
high molecular weight a difference was made between fibrinogen (in black) and immunoglobulin (in dark
gray).
out of the corona when the dextran chains are too short to hide them. On the contrary, when the
dextran chains are long enough (at least 60 kDa), the layer of adsorbed proteins can be masked in
an efficient way. The fact that protein C3 is excluded from the dextran brush and that the adsorbed
proteins are masked by the dextran brush appeared as essential factors in hindering the activation of
protein C3 of the complement system when considering dextran-coated nanoparticles.
A few conclusions can be drawn from the work done on dextran-coated PACA nanoparticles.
While proteins were adsorbed to the hydrophobic core of the nanoparticles, the characteristics of
the dextran corona controlled both the type of proteins that were adsorbed and subsequent events,
including the activation of the complement system. A dense and thick dextran brush is needed to
hinder the activation of the complement system. Besides the activation of the complement system,
the composition of the adsorbed proteins can be modulated by varying the structure and charac-
teristics of the corona. It is noteworthy that small changes can greatly influence the composition of
the adsorbed proteins as illustrated by the comparison of protein adsorbed onto nanoparticles A1
and A2 (Figure 18.5). All the results obtained from the analysis of protein interactions with our
nanoparticles coated with dextran chains suggested that the control of the adsorption of proteins is
achieved by a similar mechanism to that described with PEG nanoparticles being mainly governed
by a steric effect.
In contrast to dextran-coated nanoparticles, the nanoparticles coated with charged polysaccha-
rides behaved very differently. Nanoparticles with brushes of chitosan, heparin, and dextran-sulfate
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