B16 Membrane-Coated Vesicles for Combined Photodynamic Therapy and Immunotherapy Shift Immune Microenvironment of Melanoma

B16 膜包被囊泡用于联合光动力疗法和免疫疗法改变黑色素瘤的免疫微环境

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作者:Yuqian Wang #, Zhilong Zhao #, Chenlu Liu, Miao Hao, Chenfei Kong, Xiaoming Zhao, Yiyao Gao, Yucheng Zhang, Wanxing Cui, Congxiao Zhang, Jinlan Jiang

Conclusion

The results show that the I@BM NVs are feasible drugs for the treatment of melanoma by inducing cell apoptosis under NIR and shifting the immunosuppressive tumor microenvironment in vivo.

Methods

ICG was coated with B16 cell membranes (I@BM NVs) by sonication and extrusion, and the morphological characteristics of I@BM NVs were evaluated by transmission electron microscopy (TEM) and NP-tracking analysis. Homologous cellular uptake was evaluated by flow cytometry (FCM) after staining by DiD dye. Cellular cytotoxicity was evaluated by cell counting kit-8 assay and the anti-tumor effect in vitro was assessed by FCM and western blotting. The anti-tumor effect in vivo was evaluated in a B16 xenograft model in mice. The tumor micro-environment was investigated by FCM and real-time PCR.

Results

The vesicles are stable and uniform in nature, and show strong homologous targeting in vivo and in vitro. The vesicles can generate reactive oxygen species to induce apoptosis of B16 cells under near-infrared irradiation. Furthermore, the I@BM NVs induce a significant anti-tumor response in vivo, and perform better with respect to both tumor growth inhibition and lifespan extension. Analysis of immunocytes in the tumor microenvironment showed significant reductions in numbers of myeloid-derived suppressor cells and tumor-associated M2 macrophages in mice in the I@BM NVs group. This was accompanied by significant increases in numbers of M1 macrophages and proliferative CD4+/CD8+ T cells. Expression levels of IFN-γ and IL-2 increased in the I@BM NVs group, while expression of TGF-β and IL-10 decreased.

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