Biosynthetic Dendritic Cell-Exocytosed Aggregation-Induced Emission Nanoparticles for Synergistic Photodynamic Immunotherapy
Biosynthetic Dendritic Cell-Exocytosed Aggregation-Induced Emission Nanoparticles for Synergistic Photodynamic Immunotherapy
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DOI：
10.1021/acsnano.2c03597
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发表时间：
2022-08-12
期刊：
影响因子：
17.1
通讯作者：
Wang, Yuebing
中科院分区：
文献类型：
--
作者：
Cao, Hongmei;Gao, Heqi;Wang, Yuebing
树突状细胞（DC）衍生的小细胞外囊泡（DEV）被认为是DC疫苗的一种非常有前途的替代品;然而，基于DEV的免疫疗法的临床试验显示出有限的治疗效果。在本文中，我们开发了一种简单的策略，其中DC作为细胞反应器，以按比例放大的产量外排高效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疗法。外切的DEV-AIE NP不仅继承了来自亲本DC的免疫调节蛋白，使得T细胞活化，而且还继承了负载的AIE-光敏剂MBPN-TCyP，通过选择性地在肿瘤细胞的线粒体中积累来诱导上级免疫原性细胞死亡（ICD）。最终，DEV-AIE协同光动力免疫疗法激发了显著的免疫应答，并有效根除原发性肿瘤、远处肿瘤和肿瘤转移。此外，4 T1和CT 26实体瘤中的癌症干细胞（CSC）被免疫功能性DEVAIE NP显著抑制。我们的工作提出了一种用于细胞生成EV仿生NP的简便方法，并证明了DEV和AIE光敏剂的整合是生产临床抗癌纳米疫苗的有力方向。
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 DEVAIE 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.