是敌是友？纳米粒在炎症性肠病治疗中的功能

纳米技术广泛用于疾病诊断、预防和治疗，纳米材料的生物安全性也被日益关注。作为纳米生物安全性研究的重点，纳米材料与炎症的关系尚无统一定论（促炎/抑炎）。本课题组前期研究表明，纳米粒作用于肠道上皮可引起Wnt/β-catenin通路激活（利于肠道干细胞（ISCs）增殖与分化）；可导致基底侧胞外囊泡（EVs）组成和功能改变，发生间质-上皮样转化。基于上述效应有利于肠道黏膜和免疫微环境修复，本项目拟集中研究纳米粒在炎症性肠病（IBD）发展中的作用。首先构建不同性质的纳米粒，研究其在IBD动物、类器官、共培养细胞模型上对Wnt/β-catenin通路、ISCs增殖和分化、免疫因子和细胞的影响，阐明纳米粒在IBD肠道黏膜和免疫微环境损伤/修复中的意义，即回答纳米粒在IBD治疗中“是敌是友”的问题，为用于IBD治疗的纳米药物递送系统设计与应用提供理论指导。该项目创新性强，工作基础扎实，完成任务可行性高。

Nanotechnique has been widely used in the diagnosis, prevention and treatment of diseases, and the biosafety of nanomaterials is also increasingly concerned. As one of the key points of nano-biosafety, the relationship between nanomaterials and inflammation (proinflammatory/anti-inflammatory) has not been established. The previous research of our group shows that, the effect of nanoparticles on intestinal epithelium can cause the activation of Wnt/β-catenin signaling pathway (beneficial to differentiation and proliferation of intestinal stem cells (ISCs)); change the composition and function of basolateral extracellular vesicles (EVs), leading to mesenchymal epithelial transiton. Because these effects benefit to the restore of intestinal mucosa and immune microenvironment, this project will focus on the role of nanoparticles in the development of inflammatory bowel disease (IBD). First, we will construct nanoparticles with different properties, then investigate their effects on Wnt/β-catenin signaling pathway, ISCs differentiation and proliferation, the state of immunocytokines and immune cell, to clarify the role of nanoparticles in damage/repair of intestinal mucosa and immune microenvironment in IBD. That is to answer the question that nanoparticles are “Friend or Foe” in the treatment of IBD, which will provide theoretical guidance for the design and application of nano drug delivery system for IBD treatment. The project has obvious novelty, with solid foundation and we have great possibility to accomplish the project.