Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials

Debamitra Dutta, Shanmugavelayutham Kamakshi Sundaram, Justin Gary Teeguarden, Brian Joseph Riley, Leonard Sheldon Fifield, Jon Morrell Jacobs, Shane Raymond Addleman, George Kaysen, Brij Mohan Moudgil, Thomas Joseph Weber

Research output: Contribution to journalArticle

340 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)303-315
Number of pages13
JournalToxicological Sciences
Volume100
Issue number1
DOIs
StatePublished - Nov 2007

Fingerprint

Carbon Nanotubes
Nanostructures
Single-walled carbon nanotubes (SWCN)
Bioactivity
Nanostructured materials
UCON 50-HB-5100
Silicon Dioxide
Proteins
Albumins
Adsorption
Toxicity
Blood Proteins
Scavenger Receptors
Poloxamer
Cyclooxygenase 2
Anti-Inflammatory Agents
Acetylglucosaminidase
Macrophages
Poisons
Nonionic surfactants

Keywords

  • Albumin
  • Carbon nanotube
  • Inflammation
  • Scavenger receptor

ASJC Scopus subject areas

  • Toxicology

Cite this

Dutta, D., Sundaram, S. K., Teeguarden, J. G., Riley, B. J., Fifield, L. S., Jacobs, J. M., ... Weber, T. J. (2007). Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. Toxicological Sciences, 100(1), 303-315. https://doi.org/10.1093/toxsci/kfm217

Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. / Dutta, Debamitra; Sundaram, Shanmugavelayutham Kamakshi; Teeguarden, Justin Gary; Riley, Brian Joseph; Fifield, Leonard Sheldon; Jacobs, Jon Morrell; Addleman, Shane Raymond; Kaysen, George; Moudgil, Brij Mohan; Weber, Thomas Joseph.

In: Toxicological Sciences, Vol. 100, No. 1, 11.2007, p. 303-315.

Research output: Contribution to journalArticle

Dutta, D, Sundaram, SK, Teeguarden, JG, Riley, BJ, Fifield, LS, Jacobs, JM, Addleman, SR, Kaysen, G, Moudgil, BM & Weber, TJ 2007, 'Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials', Toxicological Sciences, vol. 100, no. 1, pp. 303-315. https://doi.org/10.1093/toxsci/kfm217
Dutta D, Sundaram SK, Teeguarden JG, Riley BJ, Fifield LS, Jacobs JM et al. Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. Toxicological Sciences. 2007 Nov;100(1):303-315. https://doi.org/10.1093/toxsci/kfm217
Dutta, Debamitra ; Sundaram, Shanmugavelayutham Kamakshi ; Teeguarden, Justin Gary ; Riley, Brian Joseph ; Fifield, Leonard Sheldon ; Jacobs, Jon Morrell ; Addleman, Shane Raymond ; Kaysen, George ; Moudgil, Brij Mohan ; Weber, Thomas Joseph. / Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. In: Toxicological Sciences. 2007 ; Vol. 100, No. 1. pp. 303-315.
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