Nanoparticles for the optical imaging of tumor E-selectin.
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.
Funovics
Martin
M
Department of Angiography and Interventional Radiology, Vienna Medical University, Vienna, Austria.
Montet
Xavier
X
Reynolds
Fred
F
Weissleder
Ralph
R
Josephson
Lee
L
D000818:Animals; D002232:Carbocyanines / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D019040:E-Selectin / Q000096:biosynthesis* / Q000737:chemistry; D004492:Edetic Acid / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000378:metabolism; D012680:Sensitivity and Specificity; D013379:Substrate Specificity; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D019040:E-Selectin; D007375:Interleukin-1; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C089187:cyanine dye 3; D004492:Edetic Acid