Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases.
Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases.
复制标题
DOI：
10.1016/j.biomaterials.2016.02.028
复制
发表时间：
2016-05
期刊：
影响因子：
14
通讯作者：
F. Tansi;R. Rüger;Claudia Böhm;R. Kontermann;U. Teichgraeber;A. Fahr;I. Hilger
中科院分区：
文献类型：
--
作者：
F. Tansi;R. Rüger;Claudia Böhm;R. Kontermann;U. Teichgraeber;A. Fahr;I. Hilger
尽管有深入的研究和医学进步，转移性疾病仍然是癌症患者最常见的死亡原因。这是由于手术中诊断较晚，治疗反应差，未发现微转移和肿瘤边缘。克服这些挑战的一种方法是荧光成像，它利用荧光探针的特性，在转化开始时诊断检测分子结构，并在术中实时检测转移和肿瘤边缘。考虑到这些好处，许多造影剂适合荧光成像已被报道。然而，大多数报告只展示了原发肿瘤的检测，而不是转移瘤的检测及其在图像引导手术模型中的应用。在这项工作中，我们证明了成纤维细胞激活蛋白（FAP）对纤维肉瘤细胞转移潜能的影响，并阐明了可激活的FAP靶向免疫脂质体（FAP- il）在小鼠模型中用于图像引导检测自发转移的有效性。此外，我们表征了脂质体荧光成分在小鼠器官中的生物分布和细胞定位，并追踪了它们随时间在尿液和粪便中的排泄情况。综上所述，可激活的FAP-IL增强了术中转移灶的成像。它们在转移灶中大量积聚，随后在胆管和肝库普弗细胞中定位，并在粪便中适当排泄，证实了它们作为术中成像造影剂的效力。
Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery.In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging.