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


METHODS
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.
Yang
Lily
L
Department 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
Peng
Xiang-Hong
XH
Wang
Y Andrew
YA
Wang
Xiaoxia
X
Cao
Zehong
Z
Ni
Chunchun
C
Karna
Prasanthi
P
Zhang
Xinjian
X
Wood
William C
WC
Gao
Xiaohu
X
Nie
Shuming
S
Mao
Hui
H
D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011859:Radiography; D055293:Receptors, Urokinase Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared
D005290:Ferric Compounds; D055293:Receptors, Urokinase Plasminogen Activator; C000499:ferric oxide