Contact activation of kallikrein-kinin system by superparamagnetic iron oxide nanoparticles in vitro and in vivo

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Previously we reported that plasma kallikrein and high molecular weight kininogen attach to the surface of dextran-coated superparamagnetic iron oxide nanoparticles (SPION) through the incompletely covered iron oxide core (Simberg et al., Biomaterials, 2009). Here we show that SPION also activate kallikrein-kinin system in vitro and in vivo. The serine protease activity of kallikrein was stably associated with SPION and could be detected on the nanoparticles even after extensive washing steps. The enzymatic activity was not detectable in kininogen-deficient and Factor XII-deficient plasma. The enzymatic activation could be blocked by precoating SPION with histidine-rich Domain 5 (D5) of kininogen. Importantly, the kallikrein activity was detectable m plasma of SPION-injected, but not of D5/SPION-injected mice. Tumor-targeted SPION when injected into kininogen-deficient and control mice, produced high levels of vascular clotting in tumors, suggesting that kallikrein activation is not responsible for the nanoparticle-induced thrombosis. These data could help in understanding the toxicity of nanomaterials and could be used in designing nanoparticles with controlled enzymatic activity. (C) 2009 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2009-12
Language
English
Article Type
Article; Proceedings Paper
Keywords

THROMBOSIS; DELIVERY

Citation

JOURNAL OF CONTROLLED RELEASE, v.140, no.3, pp.301 - 305

ISSN
0168-3659
DOI
10.1016/j.jconrel.2009.05.035
URI
http://hdl.handle.net/10203/98835
Appears in Collection
BiS-Journal Papers(저널논문)
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