Different Effect of Hydrogelation
on Antifouling and
Circulation Properties of Dextran–Iron Oxide Nanoparticles
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Abstract
Premature recognition and clearance of nanoparticulate
imaging
and therapeutic agents by macrophages in the tissues can dramatically
reduce both the nanoparticle half-life and delivery to the diseased
tissue. Grafting nanoparticles with hydrogels prevents nanoparticulate
recognition by liver and spleen macrophages and greatly prolongs circulation
times in vivo. Understanding the mechanisms by which hydrogels achieve
this “stealth” effect has implications for the design
of long-circulating nanoparticles. Thus, the role of plasma protein
absorption in the hydrogel effect is not yet understood. Short-circulating
dextran-coated iron oxide nanoparticles could be converted into stealth
hydrogel nanoparticles by cross-linking with 1-chloro-2,3-epoxypropane.
We show that hydrogelation did not affect the size, shape and zeta
potential, but completely prevented the recognition and clearance
by liver macrophages <i>in vivo</i>. Hydrogelation decreased
the number of hydroxyl groups on the nanoparticle surface and reduced
the binding of the anti-dextran antibody. At the same time, hydrogelation
did not reduce the absorption of cationic proteins on the nanoparticle
surface. Specifically, there was no effect on the binding of kininogen,
histidine-rich glycoprotein, and protamine sulfate to the anionic
nanoparticle surface. In addition, hydrogelation did not prevent activation
of plasma kallikrein on the metal oxide surface. These data suggest
that (a) a stealth hydrogel coating does not mask charge interactions
with iron oxide surface and (b) the total blockade of plasma protein
absorption is not required for maintaining iron oxide nanoparticles’
long-circulating stealth properties. These data illustrate a novel,
clinically promising property of long-circulating stealth nanoparticles