线粒体靶向性碳点基荧光探针的构筑及癌症诊疗一体化研究

At present, cancer is one of the major diseases to threaten the human life and health seriously in the world. Early diagnose and timely therapy is the pivotal to prevent and cure the cancer. Novel carbon dots (CDs) provide a new opportunity for early diagnose and therapy of cancer, so developing tumor-targetable and high-sensitivity CDs fluorescent nanoprobe, which possess theoretic importance and potential application value. The project focuses on the synthesis and preparation of a serious of CDs with good biocompatibility and photoluminescence properties. Based on the characteristics of the mitochondria membrane potential in cancer cells increased significantly, some important active molecules with targeting recognition mitochondria are conjugated to the surface of CDs by chemical reaction for functional modification, which design and fabricate the high-sensitivity mitochondria-targetable nanoprobe and applied in super-resolution cellular and subcellular imaging. Then some anticancer drugs are grafted and copolymerized to the surface of nanoprobe to construct theranostic nanosystem of cancer, which possess high sensitivity, exquisite targeting, high curative effect, stabilized and low mammalian toxicity. Moreover, the as-constructed theranostic nanosystem are further applied for tumor diagnosis and treatment in vivo. This research will contribute to providing new methods and technologies for early accurate diagnosis and high-efficiency precise therapy of cancer.

癌症是全球范围内威胁人类生命健康的重大疾病之一。早期诊断和治疗是预防、治愈癌症的关键。新型碳量子点为癌症的早期诊断和治疗提供了新的机遇，发展靶向癌细胞的高灵敏度碳点荧光探针不仅具有理论意义且有潜在的应用价值。本项目拟制备一系列生物相容性好、发光性能优良的碳点，将一些线粒体靶向识别活性分子通过化学作用共价结合于碳点表面进行功能化，基于癌细胞内线粒体膜电位显著提高的特性，设计合成高灵敏度线粒体靶向性碳点荧光探针，用于超分辨亚细胞和细胞成像研究；在此基础上将抗癌药物接枝共聚到探针表面，构建高灵敏度、高靶向、高疗效、稳定和低毒副作用的癌症“诊疗一体化”纳米体系，在活体层面上开展肿瘤诊疗研究，为实现癌症早期精确诊断和高效精准治疗提供新方法和新技术。

早期诊断和治疗是预防、治愈癌症的关键。新型碳点具有尺寸小、发光性能强和生物相容性好等优点，为癌症的早期诊断和治疗提供了新机遇。该项目研制了一系列多色荧光碳点，运用透射电镜、原子力显微镜、荧光、紫外、光电子能谱、红外等对其进行表征，构建了线粒体靶向性碳点基荧光探针和“诊疗一体化”纳米体系，考察探针和纳米体系的发光特性、稳定性、细胞毒性等，研究其作用机理并应用于细胞内线粒体成像和体内抗肿瘤治疗。构筑了检测不同目标物的碳点荧光探针，用于药品、食品、血样、尿样、环境水样等实际样品的定量检测。项目取得了一些重要结果：（1）构建了线粒体靶向性碳点基荧光探针，建立了灵敏检测癌细胞内线粒体的荧光传感新方法，成功实现荧光增强的线粒体成像检测，为癌症早期诊断提供了一种新的分析方法；（2）构筑了“诊疗一体化”纳米体系，药物喜树碱的负载率高达64.6%，具有谷胱甘肽刺激响应释放的性能，深入探讨了该纳米体系在细胞和活体内释放药物的机理，成功用于癌细胞内线粒体靶向成像和活体抗肿瘤治疗，为“诊疗一体化”纳米体系的发展提供了新方法和新技术；（3）构筑了诸多检测药物、氨基酸、金属离子、阴离子、pH等的高灵敏荧光分析方法，探讨了碳点与目标物相互作用的机理，为探针设计提供指导思想，拓宽了碳点在分析检测领域的应用范围；（4）研制了不同颜色发光效率高的碳点，详细研究了它们的发光机理，为碳点的可控制备开拓了新思路。项目已发表SCI论文38篇，中文论文1篇，其中二区及以上论文26篇，代表性研究工作发表在ACS Applied Materials & Interfaces, ACS Sustainable Chemistry & Engineering, Sensors and Actuators B: Chemical, Chemistry of Materials, Journal of Materials Chemistry B, Food Chemistry等国际期刊上。Food Chemistry上的论文发表两月即被评为ESI 1%高被引论文。本项目丰富了碳点的种类，拓宽了碳点的应用范围，构筑的靶向识别癌细胞内线粒体的荧光探针及“诊疗一体化”纳米体系为癌症早期精确诊断和高效精准治疗提供了新方法和新技术。项目的顺利实施将为促进碳点在生物医学领域的应用提供有效支持。