碳点支持金属SERS探针诱导癌相关成纤维细胞自噬机制及抗肿瘤研究

癌相关成纤维细胞(CAFs)作为肿瘤微环境中的重要组成部分对肿瘤的生长、转移及耐药等起着关键作用；其中，细胞自噬是CAFs在行使肿瘤促进功能时采用的重要机制。通过调控CAFs自噬有望实现对肿瘤的有效治疗。另一方面，纳米材料与细胞相互作用时常常会诱导细胞发生自噬，这一现象也在近年被利用于肿瘤的纳米治疗设计。然而，纳米材料与自噬相关分子的相互作用机制，以及其诱导CAFs自噬的模式都还不是很明确。本项目拟在前期基于表面增强拉曼光谱(SERS)技术的CAFs和细胞自噬研究的基础上，构建碳点支持的金纳米结构(Au@CDs)来诱导CAFs自噬，研究其自噬模式和细胞分泌情况；同时利用Au@CDs良好的SERS活性在自噬途径中原位构筑免疫SERS体系以分析其与自噬分子的相互作用。进而组装针对CAFs的Au@CDs靶向探针，结合Au@CDs的近红外吸收特性，实现靶向肿瘤微环境和由自噬介导的肿瘤光热治疗。

Cancer-associated fibroblasts (CAFs), one of the most important components in tumor microenvironment, play a key role in tumor growth, metastasis and drug resistance. Among them, autophagy is an important molecular mechanism used by CAFs in tumor promotion. By regulating CAFs autophagy, it is expected to achieve effective treatment of tumor. On the other hand, nanomaterials often induce autophagy when they interact with cells, which has also been used in the design of nanotherapy for cancer in recent years. However, the mechanism of interaction between nanomaterials and autophagy related molecules, as well as the model of CAFs autophagy induced by nanomaterials are not clear. In this project, on the basis of CAFs and autophagy research based on surface enhanced Raman spectroscopy (SERS) technology, carbon-dot-supported gold nanostructures (Au@CDs) will be fabricated to induce the autophagy of CAFs and study the autophagy mode and cellular secretion. Meanwhile, Au@CDs also show good SERS activity which is beneficial for constructing in situ immuno-SERS system to analyze the interaction between Au@CDs with autophagy molecules. Furthermore, CAFs-targeted nanoprobe based on Au@CDs will be fabricated and combined with the near infrared absorption characteristics of Au@CDs to realize the autophagy mediated photothermal tumor therapy.