ToxSci Advance Access originally published online on August 19, 2007
Toxicological Sciences 2007 100(1):303-315; doi:10.1093/toxsci/kfm217
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Adsorbed Proteins Influence the Biological Activity and Molecular Targeting of Nanomaterials
* Particle Engineering Research Center and the Department of Materials Science and Engineering, University of Florida, Gainesville, Florida 32611
Advanced Processing and Applications Group
Biological Monitoring and Modeling
Process Science and Engineering, Environmental Technology Directorate
¶ Biological Systems Analysis and Mass Spectrometry, Pacific Northwest National Laboratory, Richland, Washington 99354
|| Division of Nephrology, Department of Medicine and the Department of Biochemistry and Molecular Medicine, University of California, Davis, California 95616, and the Department of Veteran's Affairs, Northern California Health Care System, Mather, California 95655
||| Cell Biology and Biochemistry, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 99354
1 To whom correspondence should be addressed at the Department of Cell Biology and Biochemistry, Pacific Northwest National Laboratory, 790 6th Street, P7-56, Richland, WA 99354. Fax: (509) 376-6767. E-mail: thomas.weber{at}pnl.gov.
Received May 11, 2007; accepted August 9, 2007
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Abstract |
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The possible combination of specific physicochemical properties operating at unique sites of action within cells and tissues has led to considerable uncertainty surrounding nanomaterial toxic potential. We have investigated the importance of proteins adsorbed onto the surface of two distinct classes of nanomaterials (single-walled carbon nanotubes [SWCNTs]; 10-nm amorphous silica) in guiding nanomaterial uptake or toxicity in the RAW 264.7 macrophage–like model. Albumin was identified as the major fetal bovine or human serum/plasma protein adsorbed onto SWCNTs, while a distinct protein adsorption profile was observed when plasma from the Nagase analbuminemic rat was used. Damaged or structurally altered albumin is rapidly cleared from systemic circulation by scavenger receptors. We observed that SWCNTs inhibited the induction of cyclooxygenase-2 (Cox-2) by lipopolysaccharide (LPS; 1 ng/ml, 6 h) and this anti-inflammatory response was inhibited by fucoidan (scavenger receptor antagonist). Fucoidan also reduced the uptake of fluorescent SWCNTs (Alexa647). Precoating SWCNTs with a nonionic surfactant (Pluronic F127) inhibited albumin adsorption and anti-inflammatory properties. Albumin-coated SWCNTs reduced LPS-mediated Cox-2 induction under serum-free conditions. SWCNTs did not reduce binding of LPSAlexa488 to RAW 264.7 cells. The profile of proteins adsorbed onto amorphous silica particles (50–1000 nm) was qualitatively different, relative to SWCNTs, and precoating amorphous silica with Pluronic F127 dramatically reduced the adsorption of serum proteins and toxicity. Collectively, these observations suggest an important role for adsorbed proteins in modulating the uptake and toxicity of SWCNTs and nano-sized amorphous silica.
Key Words: scavenger receptor; albumin; carbon nanotube; inflammation.
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