Nanoparticles for the optical imaging of tumor E-selectin

Neoplasia. 2005 Oct;7(10):904-11. doi: 10.1593/neo.05352.

Abstract

We designed a fluorescent peptide-magnetic nanoparticle conjugate that images E-selectin expression in mouse xenograft models of Lewis lung carcinoma (LLC) by fluorescence reflectance imaging. It was synthesized by attaching the E-selectin-binding peptide (ESBP; CDSDSDITWDQLWDLMK) to a CLIO(Cy5.5) nanoparticle to yield ESBP-CLIO(Cy5.5). Internalization by activated human umbilical vein endothelial cells (HUVECs) was rapid and mediated by E-selectin, indicated by the lack of uptake of nanoparticles bearing similar numbers of a scrambled peptide (Scram). To demonstrate the specificity of E-selectin targeting to ESBP-CLIO(Cy5.5) in vivo, we coinjected ESBP-CLIO(Cy5.5) and Scram-CLIO(Cy3.5) and demonstrated a high Cy5.5/Cy3.5 fluorescence ratio using the LLC. Histology showed that ESBP-CLIO was associated with tumor cells as well as endothelial cells, but fluorescence-activated cell sorter analysis showed a far less expression of E-selectin on LLC than on HUVECs. Using immunohistochemistry, we demonstrated E-selectin expression in both endothelial cells and cancer cells in human prostate cancer specimens. We conclude that ESBP-CLIO(Cy5.5) is a useful probe for imaging E-selectin associated with the LLC tumor, and that E-selectin is expressed not only on endothelial cells but also on LLC cells and human prostate cancer specimens.

Publication types

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

MeSH terms

  • Animals
  • Carbocyanines / pharmacology
  • Carcinoma, Lewis Lung / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Separation
  • E-Selectin / biosynthesis*
  • E-Selectin / chemistry
  • Edetic Acid / chemistry
  • Endothelial Cells / cytology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / pathology
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / metabolism
  • Male
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Nanostructures* / chemistry
  • Nanotechnology / methods*
  • Neoplasm Transplantation
  • Peptides / chemistry
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis
  • Prostatic Neoplasms / metabolism
  • Sensitivity and Specificity
  • Substrate Specificity
  • Time Factors
  • Umbilical Veins / cytology

Substances

  • CY5.5 cyanine dye
  • Carbocyanines
  • E-Selectin
  • Interleukin-1
  • Peptides
  • Platelet Endothelial Cell Adhesion Molecule-1
  • cyanine dye 3
  • Edetic Acid