5篇国自然中标项目标书中英文摘要

一题目：基于细胞膜纳米囊泡的肝癌疫苗递送系统的设计、构建及性能研究项目类别：联合基金项目申请代码：L02批准年度：2017中文摘要：肝癌死亡率居福建省所有恶性肿瘤之首，外科手术适应症有限且易复发，亟需结合肝癌免疫治疗以提高病人长期生存质量。

设计和构建安全高效的肝癌疫苗递送系统是实现肝癌免疫治疗的关键问题。

本项目拟在课题组创建的细胞膜抗原展示纳米平台基础上，发展新型肝癌疫苗递送系统：采用基因工程方法在细胞膜表面定向表达肝癌抗原多肽；自组装制备纳米囊泡并负载分子影像探针，实现多模态影像监测下的肝癌免疫治疗。

系统揭示纳米囊泡的化学组成、微观结构、稳定性与免疫原性之间的规律，阐明其组装原理和作用机制。

通过对肝癌免疫治疗的无创、实时、多模态成像分析，明确治疗引起的影像学特征的病理学基础及其分子机制，创建免疫治疗监控的分子影像学评估方案并优化纳米囊泡载体系统。

本项目实施可望获得一类具有我国自主知识产权、潜在临床价值的多功能集成肝癌疫苗纳米递送系统，为探索肝癌疫苗纳米递送载体的设计与构建原理并发展具有临床应用价值的肝癌疫苗奠定基础。

英文摘要：The mortality rate of hepatocellular carcinoma is ranked Top one in Fujian province and has received increasing attention. In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for hepatocellular carcinoma. Its premise is based on harnessing the power of the host immune system to destroy cancer cells. Development of immune-mediated therapies, such as nanovaccines, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced hepatocellular carcinoma immunotherapy. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with hepatocellular carcinoma. Recently, cell plasma membrane derived vesicles (CMVs) have attracted lots of attention for their potential roles as drug carriers for immune-mediated therapies. As naturally derived materials, CMVs are completely biocompatible which makes them the idea nanoplatform forimmunotherapy purposes. Here we aim to develop a nanoplatform technology that can solve the challenges in the fabrication and engineering of CMVs for hepatocellular carcinoma immunotherapy. Specifically, we will fabricate CMVs by self-assembly of purified cell membrane extract, mainly lipid rafts separated from other cellular components using the density gradient. A proof-of-concept study will be performed with antigen peptide and imaging probe co-delivery with CMVs extracted from engineered cells. In addition, studies on mechanisms of immune evasion and using molecular imaging have enhanced our understanding on the immunology of hepatocellular carcinoma. Development of molecular imaging technology for high sensitivity, high-resolution multi-modality imaging will open up a broader application in early response for hepatocellular carcinoma immunotherapy. We design and prepare a series of novel targeted theranostic CMVs by using unique natural biological of CMVs, genetic expression of antigen peptides on its surface and self-assembly methods to load imaging probes, to achieve multi-modality imaging-guided hepatocellular carcinoma immunotherapy. We seek to determine and delineate the sophisticated multifunctional theranostic agents with optimized properties for arrange of related applications: efficient nanovaccine delivery, non-invasive quantitative analysis on the distribution of CMVs and early immunotherapy response in vivo. If successful, the proof-of-concept will allow for preclinical and clinical applications of CMVs in hepatocellular carcinoma immunotherapy.二题目：智能诊疗剂的制备及在PET/MRI/PA三模态成像和靶向热疗中应用研究项目类别：面上项目申请代码：E0310批准年度：2015年中文摘要：肿瘤的诊断与治疗分离是肿瘤临床主要问题之一，智能诊疗剂有望解决这个问题。

本项目拟在我们前期工作的基础上，设计和制备RGD多肽共轭的放射性核素Cu-64标记的磁性黑色素纳米诊疗剂（RGD-64Cu-MMNs），用于神经胶质瘤的PET、MRI和光声（PA）成像和靶向热疗。

利用黑色素作为模板通过仿生法控制合成磁性黑色素纳米颗粒（MMNs），然后共价偶联RGD。

利用黑色素能吸附金属离子的生物功能，对MMNs进行放射性核素Cu-64标记，实现PET成像。

同时利用MMNs超顺磁性和近红外吸收特性实现MRI和PA成像。

在成像指导下，利用MMNs在808 nm激光光照作用下的光热转换效应，达到光热治疗的效果，并深入探讨其可能机制。

本研究利用纳米技术平台创新性地将肿瘤的诊断和治疗有机地融合，有望为解决神经胶质瘤的诊断、精确定位、高效治疗、疗效实时监测等关键科学问题提供理论和技术基础。

英文摘要：Activatable theranostics are novel clinical solutions for the major issue of the separation of tumor diagnosis and treatment. Based on our previous studies, we design and prepare a RGD4C peptide conjugated radionuclide Cu-64 labelled magnetic melanin nanopaticles (RGD-64Cu-MMNs) for positron emission tomography (PET), magnetic resonance imaging (MRI), and photoacoustic (PA) tri-modal imaging guided targeting hyperthermia of U87MG glioblastoma cancer. The bioploymer melanin is used as the biotemplate to direct the synthesis of magnetic nanoparticles by biomimetic synthesis method. Then RGD4C is conjugated with MMNs. The radionuclide Cu-64 is labelled with MMNs by the high affinity of metal ions of melanin, which is employed for PET imaging. Meanwhile, the superparamagetism and near-infrared (NIR) absorbance of MMNs are used for MRI and PA imaging, respectively. Based on imaging guide, the photoactive hyperthermia effect of RGD-MMNs, upon 808 nm laser irradiation, can be used for targetedphotothermal therapy of glioblastoma cancer, as well as further investigation on the possible mechanism of the treatment. Organic fusion of multi-modal imaging and photothermal therapy based on one nanoplatform enables early diagnosis, accurate positioning, efficient therapy, real-time monitoring curative effect of glioblastoma cancer.三题目：新型光诊疗剂的制备及其在肿瘤多模式成像和治疗中的应用研究项目类别：青年项目申请代码：H2706批准年度：2014年中文摘要：肿瘤的诊断与治疗分离是肿瘤临床主要问题之一。