| 1 | Natural killer cell-derived extracellular vesicle significantly enhanced adoptive T cell therapy against solid tumors via versatilely immunomodulatory coordination显示文摘Insufficient tumor tropism,MHC classⅠmolecules(MHC-I)defects of tumor cells,and immunosuppressive tumor microenvironment(TME)seriously imperil the efficacy of adoptive T cell therapy on solid tumors.Here,natural killer cell-derived extracellular vesicle(Nev)is used as a versatile toolkit to synergistically improve adoptive T cell therapy for solid tumors.Specifically,Nev is modified with dibenzocyclooctynes(DBCO)linked with p H-sensitive benzoic-imine bonds;meanwhile,cytotoxic T lymphocyte(CTL)is decorated with azide groups.Then CTL is armed with Nev(CTL-Nev)through the click chemistry reaction.After systematic administration,Nev obviously promotes the tumor-targeting accumulation of CTL coming from its native tumor-tropism capability.Then,the cleavage of benzoic-imine bonds in the slightly acidic TME leads to the release of Nev,which not only directly induces tumor apoptosis but also promotes the action of CTL via multiplex pathways,such as up-regulating the MHC-I expression on tumor cells,reprogramming tumor-associated macrophages from pro-tumoral M2 phenotypes to tumoricidal M1 phenotypes.The all-around coordination of Nev with CTL results in potent tumor repression. | Weidong Nie Wenlin Fan Anqi Jiang Guanghao Wu Houli Liu Li-Li Huang Hai-Yan Xie | 2021 | Science China Chemistry2021，64，11： | 1 |
| 2 | MiR-93-5p in BM-MSCs-derived exosomes ameliorates renal fibrosis by affecting macrophage polarization显示文摘MiRNAs and macrophages play important roles in renal fibrosis.The exosomes secreted by bone marrow mesenchymal stem cells(BM-MSCs)can alleviate renal fibrosis.What is not clear,however,is whether a type of miRNAs in the BM-MSCs exosomes can alleviate renal fibrosis by modulating macrophage polarization.First,we take a high-throughput sequencing of miRNAs in exosomes of BM-MSCs from chronic kidney disease(CKD)and normal people.Then we used the UUO mouse model and injected exosomes into the tail vein.The macrophages were stimulated with lipopolysaccharide(LPS).MSC-Exo or exosomes from BM-MSCs transfected with miR-93-5p inhibitor(Inhi-Exo)were added to the culture medium.The macrophages were transfected with miR-93-5p inhibitor or miR-93-5p mimic alone.The expression of miR-93-5p in exosomes of CKD patients was significantly decreased compared with normal people and in the LPS-stimulated macrophages and UUO mice kidneys.After stimulation with LPS,the macrophages polarized toward M1 subtype.MSC-Exo or miR-93-5p mimic promoted macrophages from M1 to M2 subtype.Inhi-Exo or miR-93-5p inhibitor blocked the differentiation from M1 to M2 subtype.Significant fibrotic changes occurred in the kidneys of UUO mice,and M1 macrophages were significantly increased.After injecting exosomes into the tail vein of UUO mice,the degree of renal fibrosis was alleviated,the expression of miR-93-5p in the kidney was significantly increased,and the renal macrophages differentiated from M1 to M2 subtype.These results demonstrated that miR-93-5p in the exosomes derived from BM-MSCs can improve renal fibrosis by inducing macrophage differentiation from M1 to M2 subtype. | Anqi Nie Jiaqi Shi Xuerong Wang Yuqing Lu Wufei Dai Jianhua Wu Jing Liu Xiaolan Chen | 2022 | Life Research2022，5，3： | 0 |
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