如何有效提高纳米颗粒在肿瘤部位的富集而减少其在正常组织的累积，是提高抗肿瘤药效的关键；如何调控纳米颗粒结构具有肿瘤靶向，又具有高穿透能力是药物输送系统的难点。新型纳米诊疗系统的构建是实现肿瘤精准治疗与提高安全性的重要手段，其中合适的药物载体材料和制备方法是关键。本项目拟构建新型多孔AuNCs@Zein作为药物载材，引入多巴胺、抗体靶向分子等，有针对性地对其进行化学修饰和功能化，克服其靶向性、稳定性、控缓释等缺陷；以紫杉醇、喜树碱类抗癌药物纳米优势晶型为模型药物，采用超临界溶析-超声反溶剂渗析自组装技术制备AuNCs@Zein基多模式药物输送系统（DDS），通过其理化、生化性质评价，探索DDS微结构-体内循环-多重响应协同治疗性能关系；利用AuNCs独特的光学和电子学特性，实现DDS输送可视化，实时跟踪药物输送和释放过程，达到高效、安全、靶向及多模式精准癌症治疗的目的。

The core problem to improve the antitumor efficacy lies in how to effectively improve the accumulation of nanoparticles in the tumor site rather than in normal tissue, and the thorny issue for the novel nano-DDS is how to control and design the structure of nanoparticles with target delivery as well as high tumor penetration. While screening the suitable drug carrier and preparation method is the key to tackle the above problems. In this proposal, based on the nanocarrier of AuNCs@Zein, targeted chemical methods, i.e. surface coating by polydopamine, crosslinked by folate or antibody molecule, will be used for the modification of AuNCs@Zein to overcome its unstability, lack of target and controlled release. Typical anti-cancer medicines, i.e., novel nanocrystals of paclitaxel, camptothecin and their analogues, will be selected as model pharmaceuticals, and the efficient preparation methods, i.e. supercritical anti-solvent coupled with ultrasonic dialysis method, will be established to prepare AuNCs@Zein-based multi-functional drug delivery system (DDS). The physicochemical and biochemical properties of the prepared DDS will be analyzed in detail, and the relationships among DDS micro-structures, biofate and responsive synergy therapy will be explored. Delivery visualization, real-time tracking of drug release process and multi-responsive therapy will be achieved based on the unique optical and electronic features of AuNCs. The results are promising for the enhancement of theoretical basis and methods for Zein modification, its high-value utilization and AuNCs@Zein-DDS creation.