AIEgen-coupled upconversion nanoparticles eradicate solid tumors through dual-mode ROS activation
AIEgen-coupled upconversion nanoparticles eradicate solid tumors through dual-mode ROS activation
复制标题
AIEgen 耦合上转换纳米粒子通过双模式 ROS 激活根除实体瘤
DOI：
10.1126/sciadv.abb2712
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发表时间：
2020-06-01
期刊：
影响因子：
13.6
通讯作者：
Liu, Bin
中科院分区：
文献类型：
--
作者：
Mao, Duo;Hu, Fang;Liu, Bin
活性氧（Reactive oxygen species，ROS）是调节抗肿瘤免疫应答的关键，它可以诱导免疫原性细胞死亡，促进抗原呈递，激活免疫细胞。在这里，我们报告了近红外（NIR）驱动的免疫刺激剂的发展，基于耦合上转换纳米粒子与聚集诱导发射发光体（AlEgens），以整合ROS的免疫学效应，增强适应性抗肿瘤免疫反应。瘤内注射的AlEgen上转换纳米颗粒在高功率NIR照射下产生高剂量的ROS，其诱导免疫原性细胞死亡和抗原释放。这些纳米颗粒还可以捕获释放的抗原并将其递送到淋巴结。在淋巴结的后续低功率NIR治疗后，产生低剂量ROS以通过树突细胞的活化进一步触发有效的T细胞免疫应答，从而防止局部肿瘤复发和远处肿瘤生长。在AlEgen偶联的上转换纳米颗粒上的双模泵浦功率的效用提供了一个强大且可控的平台，以激活用于肿瘤免疫治疗的适应性免疫系统。
Reactive oxygen species (ROS) are essential for the regulation of antitumor immune responses, where they could induce immunogenic cell death, promote antigen presentation, and activate immune cells. Here, we report the development of near-infrared (NIR)-driven immunostimulants, based on coupling upconversion nanoparticles with aggregation-induced emission luminogens (AlEgens), to integrate the immunological effects of ROS for enhanced adaptive antitumor immune responses. Intratumorally injected AlEgen-upconversion nanoparticles produce high-dose ROS under high-power NIR irradiation, which induces immunogenic cell death and antigen release. These nanoparticles can also capture the released antigens and deliver them to lymph nodes. Upon subsequent low-power NIR treatment of lymph nodes, low-dose ROS are generated to further trigger efficient T cell immune responses through activation of dendritic cells, preventing both local tumor recurrence and distant tumor growth. The utility of dual-mode pumping power on AlEgen-coupled upconversion nanoparticles offers a powerful and controllable platform to activate adaptive immune systems for tumor immunotherapy.