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Receptor-Targeted Nanoparticles for In vivo Imaging of Breast Cancer

2009; American Association for Cancer Research; Volume: 15; Issue: 14 Linguagem: Inglês

10.1158/1078-0432.ccr-08-3289

1557-3265

Lily Yang, Xianghong Peng, Y. Andrew Wang, Xiaoxia Wang, Zehong Cao, Chunchun Ni, Prasanthi Karna, Xinjian Zhang, William C. Wood, Xiaohu Gao, Shuming Nie, Hui Mao,

Characterization and Applications of Magnetic Nanoparticles

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