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Clin Cancer Res. 2009 Jul 15;15(14):4722-32. doi: 10.1158/1078-0432.CCR-08-3289. Epub 2009 Jul 7.

Receptor-targeted nanoparticles for in vivo imaging of breast cancer.

Author information

  • 1Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, C-4088, 1365 C Clifton Road NE, Atlanta, GA 30322, USA. hmao@emory.edu

Abstract

PURPOSE:

Cell-surface receptor-targeted magnetic iron oxide nanoparticles provide molecular magnetic resonance imaging contrast agents for improving specificity of the detection of human cancer.

EXPERIMENTAL DESIGN:

The present study reports the development of a novel targeted iron oxide nanoparticle using a recombinant peptide containing the amino-terminal fragment of urokinase-type plasminogen activator (uPA) conjugated to magnetic iron oxide nanoparticles amino-terminal fragment conjugated-iron oxide (ATF-IO). This nanoparticle targets uPA receptor, which is overexpressed in breast cancer tissues.

RESULTS:

ATF-IO nanoparticles are able to specifically bind to and be internalized by uPA receptor-expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing s.c. and i.p. mammary tumors leads to the accumulation of the particles in tumors, generating a strong magnetic resonance imaging contrast detectable by a clinical magnetic resonance imaging scanner at a field strength of 3 tesla. Target specificity of ATF-IO nanoparticles showed by in vivo magnetic resonance imaging is further confirmed by near-IR fluorescence imaging of the mammary tumors using near-IR dye-labeled amino-terminal fragment peptides conjugated to iron oxide nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared with those receiving nontargeted iron oxide nanoparticles.

CONCLUSIONS:

Our results suggest that uPA receptor-targeted ATF-IO nanoparticles have potential as molecularly targeted, dual modality imaging agents for in vivo imaging of breast cancer.

PMID:
19584158
[PubMed - indexed for MEDLINE]
PMCID:
PMC2727672
Free PMC Article
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