Molecular imaging of pancreatic cancer in an animal model using targeted multifunctional nanoparticles.
Molecular imaging of pancreatic cancer in an animal model using targeted multifunctional nanoparticles.
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DOI：
10.1053/j.gastro.2009.01.006
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发表时间：
2009-05
期刊：
影响因子：
29.4
通讯作者：
Nie S
中科院分区：
文献类型：
--
作者：
Yang L;Mao H;Cao Z;Wang YA;Peng X;Wang X;Sajja HK;Wang L;Duan H;Ni C;Staley CA;Wood WC;Gao X;Nie S
识别一种能够使功能化纳米粒子有效靶向胰腺癌的配体/受体系统，对于开发新的胰腺癌检测和治疗方法具有很大的希望。尿激酶型纤溶酶原激活剂受体(UPAR)是一种在胰腺癌和肿瘤间质细胞中高表达的细胞受体，是一种利用多功能纳米粒子进行胰腺癌受体靶向成像的良好表面分子。通过将近红外染料标记的尿激酶型纤溶酶原激活剂受体结合域的氨基末端片段偶联到功能化磁性氧化铁纳米颗粒表面，设计并制备了uPAR靶向双模分子成像纳米颗粒探针。我们已经证明，全身递送uPAR靶向纳米粒导致它们在裸鼠原位移植的人胰腺癌肿瘤内选择性积聚。以uPAR为靶点的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内化，这促进了纳米颗粒在肿瘤内的分布，并增加了纳米颗粒在肿瘤中的数量和滞留。这种纳米粒子的成像特性使其能够在体内对隆起的胰腺癌病变进行光学和磁共振成像。利用可生物降解的多功能纳米颗粒靶向uPAR，可以选择性地将纳米颗粒输送到原发和转移的胰腺癌病变中。这种新型受体靶向纳米粒子是一种潜在的检测胰腺癌的分子显像剂。
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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