Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences, and Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
Center for AIE Research, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Physics and Optoelectronic Engineering, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, China.
ACS Nano. 2022 Sep 27;16(9):13992-14006. doi: 10.1021/acsnano.2c03597. Epub 2022 Aug 12.
Dendritic cell (DC)-derived small extracellular vesicles (DEVs) are recognized as a highly promising alternative to DC vaccines; however, the clinical testing of DEV-based immunotherapy has shown limited therapeutic efficacy. Herein, we develop a straightforward strategy in which DCs serve as a cell reactor to exocytose high-efficient DEV-mimicking aggregation-induced emission (AIE) nanoparticles (DEV-AIE NPs) at a scaled-up yield for synergistic photodynamic immunotherapy. Exocytosed DEV-AIE NPs inherit not only the immune-modulation proteins from parental DCs, enabling T cell activation, but also the loaded AIE-photosensitizer MBPN-TCyP, inducing superior immunogenic cell death (ICD) by selectively accumulating in the mitochondria of tumor cells. Eventually, DEV-AIE synergistic photodynamic immunotherapy elicits dramatic immune responses and efficient eradication of primary tumors, distant tumors, and tumor metastases. In addition, cancer stem cells (CSCs) in 4T1 and CT26 solid tumors were significantly inhibited by the immune functional DEV-AIE NPs. Our work presents a facile method for the cellular generation of EV-biomimetic NPs and demonstrates that the integration of DEVs and AIE photosensitizers is a powerful direction for the production of clinical anticancer nanovaccines.
树突状细胞 (DC) 衍生的小细胞外囊泡 (DEV) 被认为是 DC 疫苗的极具潜力的替代品；然而，基于 DEV 的免疫疗法的临床测试显示其治疗效果有限。在此，我们开发了一种简单的策略，其中 DC 作为细胞反应器，以规模化产量外排出高效的 DEV 模拟聚集诱导发射 (AIE) 纳米颗粒 (DEV-AIE NPs)，用于协同光动力免疫治疗。外排出的 DEV-AIE NPs 不仅继承了来自亲本 DC 的免疫调节蛋白，从而能够激活 T 细胞，而且还负载了 AIE-光敏剂 MBPN-TCyP，通过选择性地在肿瘤细胞的线粒体中积累，诱导卓越的免疫原性细胞死亡 (ICD)。最终，DEV-AIE 协同光动力免疫治疗引发了剧烈的免疫反应，并有效地根除了原发性肿瘤、远处肿瘤和肿瘤转移。此外，4T1 和 CT26 实体瘤中的癌症干细胞 (CSCs) 被免疫功能的 DEV-AIE NPs 显著抑制。我们的工作提出了一种用于细胞生成 EV 仿生 NPs 的简便方法，并证明了 DEVs 和 AIE 光敏剂的整合是生产临床抗癌纳米疫苗的有力方向。
