中文摘要
脑胶质瘤经综合治疗效果不佳,死亡率高,而其靶向治疗药物和特异靶向成像技术已成为研究热点。受体酪氨酸激酶(RTK)信号通路是调控胶质瘤发生发展的核心通路之一,RTK家族成员EphA2在胶质瘤细胞膜上高表达,在胶质瘤发生发展过程中起重要作用,为潜在诊断和治疗靶点。本项目以EphA2为靶点,制备特异性分子探针进行影像定位和边界确定。运用光声成像、microMRI和microPET等高分辨和高灵敏成像技术,结合分子生物学手段研究EphA2靶向治疗的分子机制,筛选靶向治疗分子,设计靶向EphA2可穿透血脑屏障的介孔硅包金星纳米探针,对胶质瘤进行光学/光声/MR多模态成像和分子靶向/化学/基因/光热多模式治疗,探索胶质瘤诊疗一体化新手段。本项目对建立胶质瘤精准诊断的分子影像学新方法,阐明EphA2靶向治疗的分子机制,开发胶质瘤诊疗新手段具有重大科学价值,研究结果将通过PET/MRI向临床转化。
英文摘要
Glioma has a high mortality rate with poor response to the combination therapy for cancers. Thus, developing glioma-targeting drugs and imaging technologies has become the hot research topic today. Receptor tyrosine kinase (RTK) signaling pathway plays a key role in the occurrence and development of glioma. EphA2 belongs to RTK and expresses largely on the surface of glioma membrane. The closely association with glioma makes it to be an potential therapeutic target. This project aims to develop the specific molecular targeting probes to locate the boundary of glioma based on the highly expression of EphA2 on its membrane. The imaging technologies with high resolution and sensitivity ,such as photoacoustic imaging, microMRI and microPET will be used to investigate the mechanisms underlying EphA2-targeting glioma therapy and screen the tumor-targeting molecules of therapeutic effects with the methods of molecular biology. We will construct mesoporous silica coated gold nanostars to penetrate blood-brain-barrier, to locate glioma through optical, photoacoustic and magnetic resonance imaging and to suppress the growth of glioma via molecular targeting therapy, chemotherapy, gene therapy and photothermal therapy. This work will greatly contribute to the establishment of precise diagnostic methods, the illustration of molecular mechanisms underlying the EphA2-targeting cancer therapy and the development of new theranostic strategies The outcome of this project will be directly translate to clinic practice via PET/MRI.
