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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Type 1 diabetes (T1D), which is a chronic autoimmune disease, results from the destruction of insulin‐producing β cells targeted by autoreactive T cells. The recent discovery that mesenchymal stem cell‐derived extracellular vesicles (MSC‐EVs) function as therapeutic tools for autoimmune conditions has attracted substantial attention. However, the in vivo distribution and therapeutic effects of MSC‐EVs potentiated by pro‐inflammatory cytokines in the context of T1D have yet to be established. Here, it is reported that hexyl 5‐aminolevulinate hydrochloride (HAL)‐loaded engineered cytokine‐primed MSC‐EVs (H@TI‐EVs) with high expression of immune checkpoint molecule programmed death‐legend 1 (PD‐L1) exert excellent inflammatory targeting and immunosuppressive effects for T1D imaging and therapy. The accumulated H@TI‐EVs in injured pancreas not only enabled the fluorescence imaging and tracking of TI‐EVs through the intermediate product protoporphyrin (PpIX) generated by HAL, but also promoted the proliferative and anti‐apoptotic effects of islet β cells. Further analysis revealed that H@TI‐EVs exhibited an impressive ability to reduce CD4+ T cell density and activation through the PD‐L1/PD‐1 axis, and induced M1‐to‐M2 macrophage transition to reshape the immune microenvironment, exhibiting high therapeutic efficiency in mice with T1D. This work identifies a novel strategy for the imaging and treatment of T1D with great potential for clinical application.