淋巴结是重要的外周免疫器官，诸多重要免疫反应都在其中完成，同时也是肿瘤细胞经淋巴转移的必经部位。因此基于免疫激活类核酸药物的高特异性淋巴结靶向输送技术对阻断肿瘤的淋巴转移具有重要意义。申请人前期研究中发现白芨多糖制备的凝胶可以通过特殊的输送途径输送药物进入淋巴结特有的被膜窦下巨噬细胞进而实现高特异性的淋巴结靶向输送。本项目拟在此基础上，提出非手术介入性特异靶向淋巴结免疫治疗概念，从材料学以及材料与机体相互作用的角度阐明凝胶载体靶向淋巴结的机理，对输送系统进行优化，建立可精确靶向淋巴结的智能化控释凝胶给药载体。根据被膜窦下巨噬细胞独特的生理特点以及肿瘤区域淋巴结的免疫抑制状态，选用let-7b这一具有独特免疫学效应的RNA片段，用于阻断肿瘤淋巴转移的治疗。该项目所涉及的研究基础扎实，在药物输送，肿瘤免疫治疗等领域具有重要的理论意义和应用前景。

Lymph nodes are important peripheral immune organs where numerous important immune responses happen. During the process of lymphatic metastasis, lymph nodes are also the sites where tumor cells must pass through. Therefore, it is essential to develop a new nucleic acid delivery system which can specially transfer immunostimulatory gene medicine into the lymph node to block lymphatic metastasis. In previous studies, the applicant observed Bletilla Striata polysaccharide formed hydrogel can effectively delivery nucleic acid drug into unique subcapsular sinus macrophages via a special administration approach, which achieve high specificity for targeting lymph node. On this basis, this subject proposes a non-surgical invasive lymph node targeting immunotherapy concept. The mechanism of hydrogel for targeting lymph node will be investigated via studying material itself and the interaction between material and the body. Then, we will optimize the delivery system and finally establish an intelligent gel controlled drug delivery system which can specially target lymph node. Due to the unique physiological characteristics of subcapsular sinus macrophages and the immunosuppression state of tumor regional lymph nodes, let-7b, a small RNA fragment with particular immunostimulatory ability, will be applied to block tumor lymphatic metastasis. The project has owned a solid research basis and has important theoretical significance and application prospects in the areas of drug delivery and cancer immunotherapy.