癌症研究
声动力疗法
小RNA
细胞毒性T细胞
免疫系统
免疫疗法
免疫检查点
化学
细胞凋亡
免疫原性细胞死亡
PD-L1
CTL公司*
医学
CD8型
免疫学
基因
体外
生物化学
作者
Yao Ma,Jinlin Li,Yun Zhao,Bing Hu,Yun Liu,Chaoqi Liu
标识
DOI:10.1016/j.ejpb.2022.10.017
摘要
MicroRNAs (miRNAs) is the tiny and highly conserved noncoding RNAs, regulate gene expression at the post-transcriptional level by binding to the 3'-UTR of target mRNAs. Several studies found that miR-195 plays an unavoidable role in the regulation of cell proliferation, cycle and apoptosis in hepatocellular carcinoma (HCC). Here, we constructed miR-195 and Chlorine e6 (Ce6) co-loading NBs (nanobubbles), making use of NBs as carriers to deliver miR-195 and Ce6 to mouse tumor models. Our results showed that the binding between PD-1 and PD-L1 was blocked by upregulating miR-195 expression. The analysis of CTL (Cytotoxic T Cell) immune activity in the treatment group was higher than the control group. Simultaneously, Ce6 was used as sonosensitizer to induce SDT (sonodynamic therapy) and trigger ICD (immunogenic cell death) of tumor cell via generation of ROS. Recent studies have found that ICD may further enhance anti-tumor immunity against PD-L1. Results indicated that combination treatment effectively stimulated infiltration of T cell and the activation of natural killer (NK) cells as well as the maturation of dendritic cells (DCs), and the combination treatment group exibited the highest CTL killing activity. These results indicate that a stronger antitumor immunity was triggered via combination of SDT-induced tumor cell ICD and immune checkpoint blockade of PD-1/PD-L1 mediated by upregulation of miR-195. In conclusion, we have successfully constructed an efficient delivery system with great potential to provide a new strategy for synergistic immunotherapy.
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