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Gold-peptide nanoconjugate cellular uptake is modulated by serum proteins

  • Guankui Wang, BS

      Affiliations

    • Department of Animal and Veterinary Science, University of Idaho, Moscow, Idaho, USA
  • ,
  • Madhusudhan R. Papasani, PhD

      Affiliations

    • Department of Animal and Veterinary Science, University of Idaho, Moscow, Idaho, USA
  • ,
  • Pallavi Cheguru, PhD

      Affiliations

    • Department of Animal and Veterinary Science, University of Idaho, Moscow, Idaho, USA
  • ,
  • Patrick J. Hrdlicka, PhD

      Affiliations

    • Department of Chemistry, University of Idaho, Moscow, Idaho, USA
  • ,
  • Rodney A. Hill, PhD

      Affiliations

    • Department of Animal and Veterinary Science, University of Idaho, Moscow, Idaho, USA
    • Corresponding Author InformationCorresponding author: University of Idaho, Ag-Biotechnology Building, Moscow, ID 83844.

Received 5 August 2011; accepted 22 October 2011. published online 02 November 2011.
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Abstract 

Gold nanoparticles (AuNPs, 20 nm) were conjugated with two different cysteine-terminated peptides. Radio-ligand binding studies were conducted to characterize AuNP-peptide binding, suggesting both covalent and noncovalent interactions. The interactions of serum proteins with AuNP-peptide nanoconjugates were determined using gel electrophoresis and dynamic light scattering. Serum proteins rapidly bound the nanoconjugates (15 minutes). The cellular uptake of free peptides and nanoconjugates into mouse myogenic (Sol8) cells was investigated in the absence or presence of serum. In the absence of serum, peptides presented as nanoconjugates showed significantly higher intracellular fluorescence signals compared to those in the presence of serum (P < 0.05), suggesting that serum proteins inhibit AuNP-mediated peptide delivery. The cellular uptake of nanoconjugates was also confirmed using transmission electron microscopy. These data suggest that AuNP-peptide nanoconjugates are a useful platform for intracellular delivery of therapeutics. However, a deeper understanding of the mechanisms regulating their uptake and intracellular trafficking is needed.

Graphical Abstract 

Fetal bovine serum (FBS) affects cellular uptake of nanoconjugates. The figure shows confocal fluorescence images of Sol8 cells incubated with AuNP-peptide A nanoconjugates (2 hours) in the presence (A) or the absence (B) of FBS. Fluorescence images suggest that in the absence of FBS, AuNP-mediated uptake of peptide A is enhanced. FBS proteins overcoat nanoconjugates, and this may lead to alterations to retrograde trafficking pathways.

Key words: Nanoparticles, Serum, Peptide, Gold, Cellular uptake, Retrograde trafficking

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 No conflict of interest is reported by the authors of this paper.

 This work was supported by the University of Idaho Blue Ribbon BANTech initiative.

PII: S1549-9634(11)00512-0

doi:10.1016/j.nano.2011.10.007

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