Viral nanoparticles as tools for intravital vascular imaging

Nat Med. 2006 Mar;12(3):354-60. doi: 10.1038/nm1368. Epub 2006 Feb 26.

Abstract

A significant impediment to the widespread use of noninvasive in vivo vascular imaging techniques is the current lack of suitable intravital imaging probes. We describe here a new strategy to use viral nanoparticles as a platform for the multivalent display of fluorescent dyes to image tissues deep inside living organisms. The bioavailable cowpea mosaic virus (CPMV) can be fluorescently labeled to high densities with no measurable quenching, resulting in exceptionally bright particles with in vivo dispersion properties that allow high-resolution intravital imaging of vascular endothelium for periods of at least 72 h. We show that CPMV nanoparticles can be used to visualize the vasculature and blood flow in living mouse and chick embryos to a depth of up to 500 microm. Furthermore, we show that the intravital visualization of human fibrosarcoma-mediated tumor angiogenesis using fluorescent CPMV provides a means to identify arterial and venous vessels and to monitor the neovascularization of the tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / cytology
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply
  • Chorioallantoic Membrane / cytology
  • Chorioallantoic Membrane / ultrastructure
  • Comovirus / chemistry
  • Comovirus / isolation & purification*
  • Diagnostic Imaging / instrumentation*
  • Diagnostic Imaging / methods*
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / virology
  • Fluorescent Dyes / analysis
  • Fluorescent Dyes / chemistry
  • Humans
  • Mice
  • Microcirculation
  • Nanostructures / analysis*
  • Nanostructures / chemistry
  • Neoplasms / blood supply
  • Neoplasms / pathology
  • Neovascularization, Pathologic
  • Polyethylene Glycols
  • Time Factors
  • Veins / cytology

Substances

  • Fluorescent Dyes
  • Polyethylene Glycols