Yang Lily, Mao Hui, Cao Zehong, Wang Y Andrew, Peng Xianghong, Wang Xiaoxia, Sajja Hari K, Wang Liya, Duan Hongwei, Ni Chunchun, Staley Charles A, Wood William C, Gao Xiaohu, Nie Shuming
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Gastroenterology. 2009 May;136(5):1514-25.e2. doi: 10.1053/j.gastro.2009.01.006. Epub 2009 Jan 14.
BACKGROUND & AIMS: 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.
鉴定一种能使功能化纳米颗粒有效靶向胰腺癌的配体/受体系统，对开发胰腺癌检测与治疗的新方法具有重要意义。尿激酶型纤溶酶原激活物受体（uPAR）是一种在胰腺癌和肿瘤基质细胞中高表达的细胞受体，是使用多功能纳米颗粒对胰腺癌进行受体靶向成像的优良表面分子。
通过将尿激酶型纤溶酶原激活物受体结合域的近红外染料标记氨基末端片段偶联到功能化磁性氧化铁纳米颗粒表面，设计并制备uPAR靶向双模态分子成像纳米颗粒探针。
我们已表明，全身递送uPAR靶向纳米颗粒可使其在裸鼠原位移植人胰腺癌肿瘤内选择性蓄积。uPAR靶向纳米颗粒探针与表达uPAR的肿瘤细胞和肿瘤相关基质细胞结合并随后被内化，这有助于纳米颗粒在肿瘤内分布，并增加纳米颗粒在肿瘤块中的量和滞留时间。纳米颗粒的成像特性能够对uPAR升高的胰腺癌病变进行体内光学和磁共振成像。
使用可生物降解的多功能纳米颗粒靶向uPAR可使纳米颗粒选择性递送至原发性和转移性胰腺癌病变。这种新型受体靶向纳米颗粒是一种用于检测胰腺癌的潜在分子成像剂。
