红细胞运载PFOB@PLGA用于肺癌演进的129Xe/19F磁共振成像及机制研究

肺癌是我国发病率和死亡率最高的恶性肿瘤。由于缺乏灵敏的早期诊断手段，导致患者就诊晚，总体预后不佳。本课题组自主研发了超灵敏肺部MRI系统，在国内首次实现了信号增强50000倍以上的人体肺部MRI，为探测早期肺癌的通气结构和功能提供了新的技术平台。基于以上研究成果，本项目拟制备PFOB@PLGA这一生物相容性高的多模态分子探针，并利用红细胞作为载体，以降低探针的免疫原性和肝肾蓄积，将其高效运输至肺腺癌模型鼠的肺部，通过129Xe/19F双核MRI及荧光成像，追踪肺癌演进相关的肺通气和气血交换功能异常信息，为肺癌的早诊提供灵敏、多视角、无辐射、可持续监测的新型影像学手段。对多分子影像精准定位出的病灶，应用生物信息学及分子生物学方法，进一步探究与肺癌演进相关的异常信号通路与免疫微环境改变，为肺癌的早诊提供理论依据。

Lung cancer is the most common cancer and the leading cause of cancer-related mortality in China. Due to the lack of sensitive early diagnosis methods, 70-80% of lung cancer patients are diagnosed in the late stages, resulting in a poor overall survival rate. We have applied the ultra-sensitive 129Xe MRI to the human lung for the first time in China, providing a new technology platform for detecting the microstructure and function of early lung cancer. Based on the platform, we intend to develop a fluorescent-labeled PFOB@PLGA nanoformulation as the multi-modal molecular probe for 129Xe/19F dual-modal MRI and fluorescence imaging, which has high biological compatibility. To reduce the immunogenicity of the nanoparticles and their accumulation in the liver and kidney, we will use red blood cells as carriers to deliver high concentrations of PFOB@PLGA nanoparticles to the lung of lung adenocarcinoma model mice, namely "RBC-hitchhiking (RH)". Then we could perform 129Xe/19F dual-modal MRI and fluorescence imaging of lung cancer and quantitatively evaluate pulmonary gas-exchange function and lung microstructure of mice with lung cancer. The RH-PFOB@PLGA mediated 129Xe/19F MRI of lung cancer could provide a comprehensive, sensitive and non-ionizing radiation imaging method for early diagnosis of lung cancer. Moreover, lesions accurately located by multi-molecular imaging will be resected. We will use the lesions to explore the abnormal signal pathways and immune microenvironment changes related to lung cancer progression by bioinformatics and molecular biology methods, which could provide a theoretical basis for the early diagnosis of lung cancer.