uPAR-targeted optical imaging contrasts as theranostic agents for tumor margin detection.
uPAR-targeted optical imaging contrasts as theranostic agents for tumor margin detection.
复制标题
作者：
Yang L;Sajja HK;Cao Z;Qian W;Bender L;Marcus AI;Lipowska M;Wood WC;Wang YA
通过手术完全切除肿瘤是早期癌症患者最重要的预后因素。在手术过程中识别原发肿瘤的浸润性肿瘤边缘、局部浸润的小肿瘤病灶以及新辅助治疗后的耐药残留肿瘤的能力将显着降低局部肿瘤复发的发生率并提高癌症患者的生存率。在这项研究中，我们报告尿激酶纤溶酶原激活剂（uPA）及其受体（uPAR）是配体/细胞表面靶标对，用于开发靶向光学成像探针，以增强肿瘤边界的成像对比度。 uPA 受体结合域的氨基末端片段 (ATF) 的重组肽用近红外荧光 (NIR) 染料分子标记，作为肽成像或肽缀合的纳米颗粒成像探针。在携带原位人类乳腺或胰腺肿瘤异种移植物或小鼠乳腺肿瘤的小鼠体内全身递送uPAR靶向成像探针，导致探针在肿瘤和基质细胞中积聚，从而产生用于肿瘤光学成像和肿瘤边缘识别的强信号。组织学分析表明，高水平的 uPAR 靶向纳米粒子存在于紧邻肿瘤细胞的肿瘤边缘或活性肿瘤基质中。此外，在使用uPAR靶向治疗诊断纳米颗粒进行靶向治疗后，通过光学成像，通过近红外染料标记的治疗诊断纳米颗粒在耐药肿瘤细胞中产生的成像对比度，可以检测到残留肿瘤。因此，我们的研究结果支持了开发用于图像引导手术的 uPAR 靶向成像和治疗诊断剂的潜力。
Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery.
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临床翻译的二氧化硅纳米颗粒作为以癌为标志性的探针进行图像引导的手术和干预措施。
DOI：
10.1039/c2ib20174g
发表时间：
2013-01
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Bradbury MS;Phillips E;Montero PH;Cheal SM;Stambuk H;Durack JC;Sofocleous CT;Meester RJ;Wiesner U;Patel S
通讯作者：
Patel S
影响因子：
11.5
作者：
He, Yu;Liu, Xiang-de;Li, Xiaowu
通讯作者：
Li, Xiaowu
影响因子：
46.9
作者：
Becker, A;Hessenius, C;Grötzinger, C
通讯作者：
Grötzinger, C
影响因子：
5.2
作者：
Hildenbrand, Ralf;Schaaf, Antonela
通讯作者：
Schaaf, Antonela
影响因子：
6.4
作者：
Kotzsch, Matthias;Bernt, Katharina;Luther, Thomas
通讯作者：
Luther, Thomas