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Plasma clearance of bacteriophage Qβ particles as a function of surface charge

Academic Article
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Overview

related to degree

  • Brown, Steven David, Ph.D. in Chemical Biology, Scripps Research 2004 - 2010
  • Prasuhn Jr., Duane E, Ph.D. in Chemistry, Scripps Research 2001 - 2007
  • Strable, Erica, Ph.D. in Biochemistry, Scripps Research 2000 - 2006

authors

  • Prasuhn Jr., Duane E
  • Singh, P.
  • Strable, Erica
  • Brown, Steven David
  • Manchester, Marianne
  • Finn, M.G.

publication date

  • January 2008

journal

  • Journal of the American Chemical Society  Journal

abstract

  • Self-assembled protein capsids have gained attention as a promising class of nanoparticles for biomedical applications due to their monodisperse nature and versatile genetic and chemical tailorability. To determine the plasma clearance and tissue distribution in mice of the versatile capsid of bacteriophage Qbeta, the particles were decorated with gadolinium complexes using the CuI-mediated azide-alkyne cycloaddition reaction. Interior surface labeling was engineered by the introduction of an azide-containing unnatural amino acid into the coat protein for the first time. Clearance rates were conveniently monitored by quantitative detection of Gd using inductively coupled plasma optical emission spectroscopy and were found to be inversely proportional to the number of complexes attached to the exterior surface of the particle. This phenomenon was correlated to changes in exterior surface charge brought about by acylation of surface-exposed amine groups in the initial step of the bioconjugation protocol. When primary amine groups were reintroduced by azide-alkyne coupling, the circulation time increased accordingly. These results show that nanoparticle trafficking may be tailored in predictable ways by chemical and genetic modifications that modulate surface charge.

subject areas

  • Animals
  • Azides
  • Bacteriophages
  • Capsid
  • Gadolinium
  • Heterocyclic Compounds, 1-Ring
  • Liver
  • Mice
  • Mice, Inbred BALB C
  • Models, Genetic
  • Models, Molecular
  • Molecular Conformation
  • Nanoparticles
  • Spectrophotometry
  • Surface Properties
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Identity

PubMed Central ID

  • PMC2657921

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja075937f

PubMed ID

  • 18177041
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Additional Document Info

start page

  • 1328

end page

  • 1334

volume

  • 130

issue

  • 4

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