Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials.
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 LPS(Alexa488) 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.
Dutta
Debamitra
D
Particle Engineering Research Center and the Department of Materials Science and Engineering, University of Florida, Gainesville, Florida 32611, USA.
Sundaram
Shanmugavelayutham Kamakshi
SK
Teeguarden
Justin Gary
JG
Riley
Brian Joseph
BJ
Fifield
Leonard Sheldon
LS
Jacobs
Jon Morrell
JM
Addleman
Shane Raymond
SR
Kaysen
George Alan
GA
Moudgil
Brij Mohan
BM
Weber
Thomas Joseph
TJ
D000327:Adsorption; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011134:Polysaccharides / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D015203:Reproducibility of Results; D012709:Serum Albumin / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry
D000893:Anti-Inflammatory Agents; D001798:Blood Proteins; D008070:Lipopolysaccharides; D037742:Nanotubes, Carbon; D011134:Polysaccharides; D051116:Receptors, Scavenger; D012709:Serum Albumin; D013501:Surface-Active Agents; D020442:Poloxamer; D012822:Silicon Dioxide; C007789:fucoidan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2