尿激酶受体
胰腺癌
癌症研究
间质细胞
分子成像
癌细胞
材料科学
体内
癌症
受体
化学
生物物理学
医学
生物
内科学
生物化学
生物技术
作者
Lily Yang,Hui Mao,Zehong Cao,Y. Andrew Wang,Xianghong Peng,Xiaoxia Wang,Hari Krishna Sajja,Liya Wang,Hongwei Duan,Chunchun Ni,Charles A. Staley,William C. Wood,Xiaohu Gao,Shuming Nie
出处
期刊:Gastroenterology
[Elsevier]
日期:2009-05-01
卷期号:136 (5): 1514-1525.e2
被引量:147
标识
DOI:10.1053/j.gastro.2009.01.006
摘要
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.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.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.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.
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