Receptor-Targeted Nanoparticles for In vivo Imaging of Breast Cancer

Open Access
Publisher Website
Google Scholar
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.