Molecular imaging of pancreatic cancer in an animal model using targeted multifunctional nanoparticles.
OBJECTIVE
Identification of a ligand/receptor system that enables functionalized nanoparticles to efficiently target pancreatic cancer holds great promise for the development of novel approaches for the detection and treatment of pancreatic cancer. Urokinase plasminogen activator receptor (uPAR), a cellular receptor that is highly expressed in pancreatic cancer and tumor stromal cells, is an excellent surface molecule for receptor-targeted imaging of pancreatic cancer using multifunctional nanoparticles.


METHODS
The uPAR-targeted dual-modality molecular imaging nanoparticle probe is designed and prepared by conjugating a near-infrared dye-labeled amino-terminal fragment of the receptor binding domain of urokinase plasminogen activator to the surface of functionalized magnetic iron oxide nanoparticles.


RESULTS
We have shown that the systemic delivery of uPAR-targeted nanoparticles leads to their selective accumulation within tumors of orthotopically xenografted human pancreatic cancer in nude mice. The uPAR-targeted nanoparticle probe binds to and is subsequently internalized by uPAR-expressing tumor cells and tumor-associated stromal cells, which facilitates the intratumoral distribution of the nanoparticles and increases the amount and retention of the nanoparticles in a tumor mass. Imaging properties of the nanoparticles enable in vivo optical and magnetic resonance imaging of uPAR-elevated pancreatic cancer lesions.


CONCLUSIONS
Targeting uPAR using biodegradable multifunctional nanoparticles allows for the selective delivery of the nanoparticles into primary and metastatic pancreatic cancer lesions. This novel receptor-targeted nanoparticle is a potential molecular imaging agent for the detection of pancreatic cancer.
Yang
Lily
L
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA. lyang02@emory.edu
Mao
Hui
H
Cao
Zehong
Z
Wang
Y Andrew
YA
Peng
Xianghong
X
Wang
Xiaoxia
X
Sajja
Hari K
HK
Wang
Liya
L
Duan
Hongwei
H
Ni
Chunchun
C
Staley
Charles A
CA
Wood
William C
WC
Gao
Xiaohu
X
Nie
Shuming
S
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D012680:Sensitivity and Specificity; D019265:Spectroscopy, Near-Infrared
D055293:Receptors, Urokinase Plasminogen Activator