利用同步辐射技术研究Gd@C82(OH)22调控肿瘤细胞EMT的作用机制

项目名称： 利用同步辐射技术研究Gd@C82(OH)22调控肿瘤细胞EMT的作用机制

项目编号： No.U1532122

项目类型： 联合基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 刘颖

作者单位： 国家纳米科学中心

项目金额： 66万元

中文摘要： 纳米颗粒本身作为高效低毒的治疗或诊断药物已经成为纳米药物研究的重要方向之一。Gd@C82(OH)22具有良好的抗肿瘤活性，可有效抑制肿瘤的侵袭和转移。上皮-间质转化(EMT)是上皮细胞来源肿瘤细胞获得迁移和侵袭能力的重要生物学过程。通过EMT，细胞失去上皮表型，获得较高迁移与侵袭、抗凋亡和降解细胞外基质能力等间质表型。Gd@C82(OH)22可明显改变肿瘤细胞的恶性表型，使其性质从间质细胞向上皮细胞转变。本项目将利用同步辐射及其相关技术分析细胞、肿瘤组织及生物体内的分布和准确定量，观察其随给药时间和给药浓度不同的动态变化；寻找治疗前后肿瘤细胞EMT关键分子与其分布和含量动态变化之间的关系；通过理论模拟和实验相结合，建立其影响肿瘤细胞EMT过程的信号通路；深入研究具有不同的诱导EMT过程的富勒烯衍生物之间物理化学性质的相关性，为制定抗肿瘤药的合成策略提供一定的理论基础和指导。

中文关键词： 富勒烯；上皮-间质转化；同步辐射；纳米药物；软X射线谱学显微

英文摘要： An important direction of nano-drug research is that nanoparticles themselves are used as therapeutic or diagnostic drugs. Our laboratory has reported the good antitumor and antimetastasis activity of Gd@C82(OH)22, a kind of gadolinium metallofullerenol nanoparticle. It is known that epithelial-mesenchymal transformation (EMT) is a process that produces complete loss of epithelial traits by the former epithelial cells accompanied by total acquisition of mesenchymal characteristics, such as vimentin, myosin, invasive motility, and so on. Accumulating evidence suggests a critical role in cancer progression, through which tissue epithelial cancers invade and metastasise. Cell characteristics are highly affected during EMT, resulting in altered cell-cell and cell-matrix interactions, cell motility and invasiveness. We found that Gd@C82(OH)22 could significantly change the malignant phenotype of tumor cells. In this project, we will analyse the distribution and content of Gd@C82(OH)22 in cell, tumor tissue and organisms using synchrotron radiation and the related technique. Meanwhile, we will study the mechanism of fullerene derivatives regulating EMT in vivo and in vitro and estimate the physical and chemical properties of fullerene nanomaterials which can induce EMT of epithelial cells using chemical, cell biological, molecular biological, proteomic and imaging techniques. It can help people understand the antitumor mechanism of fullerene derivatives and provide certain guidelines to formulate synthesis strategy of antineoplastic drugs.

英文关键词： fullerene;epithelial-mesenchymal transformation;synchrotron radiation;nanomedicine;Soft X-ray Spectromicroscopy