光控纳米免疫激活剂的构建及其在脑部疾病治疗中的应用研究

Microglia are the resident tissue macrophages of the central nervous system (CNS). Under a brain pathology condition, microglia will be activated and then release a series of immune factors for therapy. Thus, it has been actively considered, that controlled activation of microglia can be a therapeutic tool for brain diseases. However, unselective activation of all microglia cells in brain would likely result in significant side effects such as extensive pathologic neuroinflammation and neural damage. Meanwhile, as most of drugs for brain diseases treatment are ineffective and with side effects, it is urgent to develop new ways for effective treatment of brain diseases. This proposal aims to develop a method for targeting immunotherapy of brain diseases through controlled activation of microglia with near-infrared light (NIR) irradiation. In this proposal, we will build a NIR sensitive nanostructure, which can be triggered to release the activator of microglia under NIR irradiation. Consequently, the microglia cells near brain tumor cells can be selectively activated by controlling the irradiation position and time. The immune response of the activated microglia will kill brain tumor cells specifically. At the same time, we will monitor the activator release, microglia activation and brain tumor cell killing with multimodality imaging. All in all, the implement of the project can lead to breakthrough in developing specific and effective treatment of brain diseases.

小胶质细胞是中枢神经系统中重要的免疫功能细胞。活化的小胶质细胞产生免疫应答并释放一系列的免疫因子，对脑部疾病的自身免疫治疗具有重要意义。然而持续无选择性激活小胶质细胞所产生的免疫反应会对正常组织造成损害，引发神经炎症等副作用。本项目从高效治疗脑部疾病的重大需求出发，针对当前药物治疗效率低下、选择性差的问题，提出发展一种近红外光控激活小胶质细胞，用于特异性免疫治疗脑部疾病的方法。项目以脑胶质瘤细胞为疾病研究模型，拟构建一种近红外光控释放免疫激活剂的纳米体系，通过控制光照位点和时间，选择性激活靶点的小胶质细胞，从而引发免疫效应杀伤脑胶质瘤细胞，达到特异性治疗的目的。同时，发展多模态成像追踪激活剂释放、小胶质细胞活化以及免疫杀伤脑胶质瘤细胞的方法，深入探索治疗机制和效率。本项目的实施，将为探索脑部疾病的高效特异性治疗开辟新的思路与方法，具有重要的研究意义。

小胶质细胞是中枢神经系统中重要的免疫功能细胞，激活后的小胶质细胞产生免疫应答，释放一系列的免疫因子对于脑部疾病的治疗具有重要意义。然而持续无选择性激活小胶质细胞所产生的免疫反应能够对正常组织造成损害，引发神经炎症等副作用。本研究发展了一种近红外光控制性激活小胶质细胞，用于靶向免疫治疗脑部疾病的新方法。首先，项目研究构建了一种近红外光敏感的纳米激活剂体系，其进入小胶质细胞后，通过控制近红外光的照射位点和时间，可以选择性地激活脑小胶质细胞，从而引发免疫效应达到特异性治疗脑部疾病目的。同时，发展使用多模成像系统追踪激活剂释放、小胶质细胞活化，深入探索治疗机制和效率。该研究为探索脑部疾病的特异性治疗开辟了新的思路与方法。