肝癌术后复发是临床治疗的重大挑战。肿瘤微环境中，肝星形细胞活化成为具有促癌作用的肿瘤相关成纤维细胞(TAFs)是肝癌复发的高危因素。课题组前期研究证实TAFs通过多个信号通路促进肝癌细胞增殖和侵袭。结合我们前期已开展的术中近红外荧光成像导航技术对肝癌进行精准切除，我们设想在术中既精准识别肿瘤病灶又能量化研判TAFs活化状态，在实时整体显影状态下指导根治切除的范围和方式，有望改善肝癌整体预后。本课题拟构建双靶向显影肝癌(抗GPC3)和TAFs(抗FAP)的多光谱近红外荧光造影剂，在肝癌切除术中差异化成像肝癌及活化TAFs区域，实现术中精准导航病灶并实时动态定量评估微环境TAFs荷载。在此基础上，通过动物模型评估病灶与微环境整体显影下不同手术切除方式对肝癌预后的影响，有望改变目前肝癌手术的单一模式，有效将抑制肿瘤复发的关口前移，为肝癌精准手术提供术中实时成像导航的新理论和新方法。

Tumor recurrence rate remains high and contribute to a negative outcome in HCC patients. Tumor-associated fibroblasts (TAFs) are important components of the tumoral stroma and related to such malignant behaviors as tumor recurrence and progression. We have verified that TAFs were mediated by several signal pathways and promote cancer cell proliferation and metastasis. Moreover, FAP was the specific biomarker for targeted in TAFs .Near infrared imaging technique was utilized these years for precision hepatectomy in our team. Therefore, our hypothesis was to combine TAFs(anti-FAP nanoprobe) and HCC(anti-GPC-3 nanoprobe) dual imaging technique, achieve a real time intraoperative precise hepatectomy for HCC, which surgeons can judge not only the tumor margin and location, but also evaluate the TAFs activation real time. Based on this dual targeted imaging nanoprobe establishment, we design different surgical strategies for intraoperative imaging mode in vitro and in vivo experiments, sought to build an holistic surgery method which would consider tumor and microenvironment as whole target for removal. This research pre-prevent patients from HCC recurrence when they are undergoing surgery, which may effectively improve the outcome of HCC.