酶激活型近红外荧光/光声双模成像探针构建及肾癌手术导航初步应用

肾癌是人类常见十大恶性肿瘤之一，发展靶向肾癌的精准成像方法为获取癌症发生发展信息以及指导癌变组织的精准切除具有重要意义。基于有机分子探针的近红外Ⅱ荧光和光声成像技术为实现肾癌的精准成像指导肿瘤精准手术切除应用提供了强有力工具。针对传统近红外Ⅱ分子探针存在生物稳定性差、量子产率低、难以设计探针、成像模式单一、经肝脏代谢导致肾靶向性差等问题，本项目拟通过染料筛选和合理设计相结合的方法，以氧杂三环刚性结构作为关键分子片段，对氧杂三环中位碳原子进行保护，开发系列具有羟基等光学调控基、良好生物稳定性的高性能近红外Ⅱ染料。并以此为平台，针对肾癌细胞中异常表达的酶等生物标志物，设计系列酶激活型近红外Ⅱ双模探针，并通过化学修饰，调控探针的肾小管分泌代谢途径，构建肾癌靶向的酶激活型近红外Ⅱ双模探针用于手术导航初步应用，以实现肾癌的原位、高灵敏、高选择性的双模成像，为指导肾癌的精准手术切除提供强有力的工具。

Renal cancer is one of the ten most common malignant tumors in human beings. It is important to develop precise imaging methods in order to obtain the information of cancer occurrence and development and to guide the accurate resection of cancer tissue. Small-molecular probe based near infrared II fluorescent / photoacoustic dual-mode imaging technology can provide a powerful tool for achieving precise image guided surgical navigation of renal cancer. In view of the problems of traditional NIR II molecular probes, such as bad biological stability, low quantum yield, difficult to design probes, single imaging mode, poor renal targeting due to liver metabolism, etc., we will develop a series of high-performance near-infrared II dyes with good biological stability and optical tunable groups such as hydroxyl group by using the rigid structure of xanthene as the key molecular segment and protecting the central C atom of xanthene, through the combination of dye screening and rational design strategy. Using them as detection platform, selecting appropriate biomarkers of renal cancer to construct near-infrared II dual model probes. Through chemical modification, the renal tubular secretion and metabolism pathway of the probes will further regulated, and the enzyme activated NIR dual-modal probes targeted to renal cancer will be finally constructed for preliminary application of surgical navigation. With the probes, the in situ, high sensitive and high selective dual-mode imaging of renal cancer will be realized, which will provide a powerful tool for precise surgical resection of renal cancer.