Nanotech 2010

Mechanisms of Interactions of Iron Oxide Nanoparticles with Proteins and Immune Receptors

P. Karmali, Y. Chao, E. Ruoslahti, D. Simberg
University of California San Diego, US

Keywords: iron oxide, macrophage, hydrogel, plasma, scavenger receptor


Superparamagnetic dextran-iron oxide (SPIO) is a promising nanoparticle for imaging and treatment. SPIO is extensively opsonized by plasma proteins and is rapidly cleared from systemic circulation. The mechanisms of SPIO uptake and recognition by the body milieu are not clear. We used high-resolution differential mass spectrometry to analyze the spectrum of plasma proteins that bind to the nanoparticles. We demonstrate that SPIO interact with the biological milieu through the acidic iron oxide and the dextran coat. Each surface element attracted its own set of plasma proteins. Using knockout mice, we show that the attached plasma proteins, as well as other common opsonins, are unlikely to contribute to the clearance of SPIO. Despite the binding of proteins, iron oxide was directly recognized by macrophage scavenger receptor AI/II through binding to the acidic iron oxide core, while dextran played a masking function. The recognition of iron oxide in vitro and in vivo could be blocked by surface hydrogelation of nanoparticles. The hydrogelation did not reduce the level of metal exposure, suggesting a selective hindrance of the receptor-iron interaction. The knowledge of the interplay between the surface properties and the immune recognition will promote the development of new types of immune system evading nanomaterials.
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