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Engineered Cytokine-Primed Extracellular Vesicles with High PD-L1 Expression Ameliorate Type 1 Diabetes.

Published:20 May 2023 DOI: 10.1002/smll.202301019
Lanxing Wang, Chunxiao Qi, Hongmei Cao, Yanwen Zhang, Xing Liu, Lina Qiu, Hang Wang, Lijuan Xu, Zhenzhou Wu, Jianfeng Liu, Shusen Wang, Deling Kong, Yuebing Wang

Abstract

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.

Substances (2)

Materials
Procduct Name CAS Molecular Formula Supplier Price
5-Aminolevulinic acid hydrochloride 5451-09-2 C5H10ClNO3 693 suppliers $12.00-$1760.00
5-Aminolevulinic acid hydrochloride 5451-09-2 C5H10ClNO3 693 suppliers $12.00-$1760.00

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