本项目设计和构筑了核素64Cu无螯合剂稳定标记的脂质纳米囊，该纳米囊利用二氢卟吩e6（Ce6）和磷脂的偶联体在水中自组装形成双层纳米囊，纳米囊的空腔中负载CT成像剂碘克沙醇，核素64Cu被一步稳定标记于脂质纳米囊组成模块Ce6的四吡咯环中，避免了使用传统大环螯合剂修饰纳米囊而影响到纳米囊的表面物理化学特性。纳米囊的表面又偶联了肺癌标志分子AXL的适配体GLT21.T。在同一纳米系统内，核素64Cu产生的β+粒子和β-粒子分别发挥PET成像和肿瘤的内放疗作用，同时，β+和β-粒子产生的切伦科夫辐射（CR）又可以作为内光源，激发Ce6产生细胞毒性活性氧自由基（ROS），实现对肺癌的光动力学治疗（PDT），突破PDT对深度依赖性这一瓶颈问题。研究结果为开发具有高特异性、高灵敏度和高图像分辨率PET/CT成像及同步内放疗协同PDT的诊疗一体化制剂，实现肺癌早诊断早治疗做出重要的应用基础研究工作。

The project designed and constructed a lipid nanocapsule with chelator-free stable labeling of nuclide 64Cu. The nanocapsules formed double-layer structure by self-assembling of conjugate of chlorin e6 (Ce6) and phospholipids in water. The CT imaging agent iodixanol was loaded in the cavity of nanocapsules, the radionuclide 64Cu was stably labeled in the tetrapyrrole ring of building block Ce6 of the lipid nanocapsule by one step, avoiding the modification of the nanocapsules by the traditional macrocyclic chelating agent, which may affect the surface physical and chemical properties of the nanocapsule. Moreover, the aptamer of a lung cancer marker molecule AXL, GLT21.T, was conjugated on the surface of the nanocapsule. In a nanosystem, the β+ particles and β- particles produced by the nuclide 64Cu play the role of PET imaging and tumor internal radiotherapy, respectively, and the Cerenkov radiation (CR) produced by β+ and β- particles of 64Cu can be used as the internal light source to activate Ce6 to produce cytotoxic reactive oxygen species (ROS), enabling CR-induced photodynamic therapy (PDT) to destruct lung cancerous cells, breaking through the bottleneck of PDT depth dependence. The research results provide an important basis for the development of an integrated theranostics PET/CT imaging and synergistic therapy of internal radiotherapy and PDT agent with high specificity, high sensitivity and high image resolution for early diagnosis and treatment of lung cancer.