基于新型荧光磁性纳米颗粒的树突细胞活体靶向疫苗研究

项目名称： 基于新型荧光磁性纳米颗粒的树突细胞活体靶向疫苗研究

项目编号： No.81503026

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 金红林

作者单位： 华中科技大学

项目金额： 17.9万元

中文摘要： 体内树突细胞的不成熟状态和较低的抗原摄取效率是导致肿瘤免疫治疗效果不佳的重要原因之一。研究证实采用同步进行活体靶向抗原递送和DC激活的方式能显著改善免疫治疗效果。本项目以前期仿HDL材料能刺激DC成熟的研究为基础，拟利用成熟DC（mDC）高表达B类I型清道夫受体（SR-B1）的特点，建立一种生物相容性好，纳米粒径合适，且能同步运输肿瘤抗原多肽、免疫激活剂和光学/核磁探针的新型磁性荧光纳米疫苗，以期在活体内高效靶向淋巴结mDC，同时实现mDC的抗原递送、光学标记及协同诱导未成熟DC成熟，为肿瘤免疫治疗提供有效的方法。继而使用多模式成像技术，活体动态追踪DC靶向疫苗迁移至淋巴组织的过程、定量表征DC活化效率、在体评价其肿瘤抑制能力。因此，本项目有望建立一种安全高效的DC靶向新方法，研制出高效的体内DC靶向疫苗，为临床DC疫苗的应用提供实验依据，对促进信息科学与医学交叉研究具有重要意义。

中文关键词： 近红外荧光；荧光探针；纳米药物载体；树突细胞疫苗；多模成像

英文摘要： Following tumor immunotherapy, the in vivo inefficient antigen uptake and immature state of dendritic cells often hinder the desired therapeutic effect. It is confirmed that synchronous in vivo targeted antigen delivery and DC activation can significantly improve the immunotherapy efficacy. Previously, we found that the HDL mimetic nanoparticles have the ability to induce DC maturation. Taking advantage of the high expression of class B type I scavenger receptor in mDCs, this project aims to establish a multifunctional nanocarrier with excellent biocompatibility and mDC targeting ability for the simultaneous loading of magnetic resonance and optical imaging contrast agents, peptide antigens as well as immune-activating molecules, thus providing a valuable method for tumor immunotherapy. Along with the co-delivery of imaging contrast agents and immune- activating molecules, the dynamic in vivo tracking of DC migration, quantitative characterization of DC activation efficiency and assessment of its capability in tumor suppression will be achieved by the use of dual-modality imaging techniques. Together, the design of an efficient in vivo DC-targeting strategy and the development of an efficacious DC-targeting vaccine may provide useful experimental foundation for the clinical DC vaccine preparation and have great significance in promoting the interdisciplinary research between Information Science and Medicine.

英文关键词： Near infrared Fluorescence;Fluorescent probes;Nanocarrier;Dendritic cell-based vaccine;Multi-modality imaging