肿瘤细胞治疗研究
英文原题：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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树突状细胞（DC）来源的小细胞外囊泡（DEVs）被认为是 DC 疫苗极具前景的替代方案；然而，基于 DEV 的免疫疗法的临床测试显示出有限的治疗效果。
树突状细胞（DC）来源的小细胞外囊泡（DEVs）被认为是DC疫苗极具前景的替代方案；然而，基于DEV的免疫治疗的临床测试显示出有限的治疗效果。在此，我们开发了一种简便策略，其中DCs作为细胞反应器，以放大规模产量外泌高效DEV模拟的聚集诱导发光（AIE）纳米颗粒（DEV-AIE NPs），用于协同光动力免疫治疗。外泌的DEV-AIE NPs不仅继承了来自亲本DCs的免疫调节蛋白，能够实现T细胞激活，还携带了负载的AIE光敏剂MBPN-TCyP，通过选择性积聚在肿瘤细胞的线粒体中诱导优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，并有效根除原发肿瘤、远端肿瘤和肿瘤转移。此外，4T1和CT26实体瘤中的癌症干细胞（CSCs）被具有免疫功能的DEV-AIE NPs显著抑制。我们的工作提出了一种简便的细胞生成EV仿生NPs的方法，并证明DEVs与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 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.
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