聚集诱导双光子响应的金纳米探针用于乳腺癌的近红外荧光成像导向光动力治疗研究

The morbidity of breast cancer has been rising year by year, and there have been more young people suffering from it that inflict severe damage on women's life and health. The studies on precise diagnosis and efficient treatment of breast cancer have important scientific significance and social value. This project is aimed at solving the questions of some complex gold nanoprobes that applied in imaging diagnosis and treatment of tumor, such as the limited shooting depth, unclear treatment mechanisms. 2-3 kinds of highly selective and sensitive new gold nanoprobes , which have excellent aggregation-induced near infrared two photon response characters ,active targeting and subcellular localization, are introduced in the design and synthesis. By the near infrared two photon excitation fluorescence microscopy imaging technology platform, it realize the combination of diagnosis and treatment of cancer in space-time. And, we will deeply study the cell transmembrane, intracellular migration and accurate positioning of the as-prepared multifunctional gold nanoprobes. We explore the signal transduction and the molecular mechanism thatrelated with reactive oxygen species for apoptosis based on different nanoprobes in photodynamic therapy. The results will provide a new strategy and a new way for early diagnosis and treatment of cancer.

乳腺癌发病率不断攀升、发病年龄趋向年轻化，严重威胁着女性生命健康， 开展乳腺肿瘤的精确诊断和高效治疗具有十分重要的意义。本项目针对目前一些复合型金纳米诊疗探针(有机小分子染料负载的)存在激发光作用深度有限、治疗机制不清的现状，设计、合成2-3种灵敏度高、靶向性好、具有聚集诱导近红外双光子响应和良好的光动力效应，而且能够亚细胞器定位的功能性金纳米探针(无有机小分子染料负载的)；通过近红外激光、双光子荧光显微成像技术平台，进行乳腺肿瘤的精确诊断与光动力学治疗的高效、精准、时空性的结合研究；同时，深入研究功能探针的细胞穿膜、细胞内迁移和精确定位，探讨功能纳米探针在激光作用下诱导细胞凋亡的分子机制，为金纳米材料用于癌证的诊治提供新策略与新途径。

本项目围绕聚集诱导发光增强金纳米探针制备表征、治疗效应，并构建治疗效应与疾病诊治关联性生物活性物种分析探针，调查相关机制，开展了系统性工作。目前已取得的成果如下：（1）发展了氢键自组装功能化方法，合成具有双光子响应的手性强荧光金纳米探针Arg-ATT-Au nanocluster，该探针不仅具有较好的光敏化产生单线态氧性能力，而且能够进入癌细胞并迁移聚集，光照诱导细胞凋亡，呈现较好的荧光成像导向光动力治疗效应；（2）发展了强荧光P-R CDs，用于溶酶体亚细胞器的靶向定位成像研究；构筑了BSA-Cy-Mito、UCNPs@SiO2−CD36分析平台，用于活体水平上GSH/H2O2、信号分子CD36的动态监控；合成制备Biotin-Ebselen和Selenium Signture、BuCh-Au nanoprobe、BAS-Au nanocluster、CeO2-nanowire-BODIPY-ATP探针，联合质谱、荧光技术，用于癌症诊治关联性低分子硫醇、酶（BuChE）、蛋白活性表达谱、毒性离子测定，这些探针的发展为诊疗机制评估提供了有效的工具。另外，我们探讨了功能探针优异的性能机制原理，探索了功能材料在细胞响应、细胞内聚集、精确定位等结果，为发展金纳米材料的生物应用提供相关支撑。