2. Academic Validation
  3. Nanobubble-mediated Co-delivery of Ce6 and miR-195 for Synergized Sonodynamic and Checkpoint Blockade Combination Therapy with Elicitation of Robust Immune Response in Hepatocellular Carcinoma

Nanobubble-mediated Co-delivery of Ce6 and miR-195 for Synergized Sonodynamic and Checkpoint Blockade Combination Therapy with Elicitation of Robust Immune Response in Hepatocellular Carcinoma

  • Eur J Pharm Biopharm. 2022 Oct 25;S0939-6411(22)00245-4. doi: 10.1016/j.ejpb.2022.10.017.
Yao Ma 1,  Jinlin Li 2,  Yun Zhao 3,  Bing Hu 2,  Yun Liu 4,  Chaoqi Liu 5
Affiliations

Affiliations

  • 1 Department of Ultrasound Imaging, The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443008, China.
  • 2 Department of Ultrasound Imaging, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443000, China.
  • 3 Medical College of China Three Gorges University, Yichang, 443002, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.
  • 4 Department of Ultrasound Imaging, The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443008, China. Electronic address: [email protected].
  • 5 Medical College of China Three Gorges University, Yichang, 443002, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China. Electronic address: [email protected].
PMID: 36307001 DOI: 10.1016/j.ejpb.2022.10.017
Abstract

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, making use of NBs (nanobubbles) 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 further triggered a strong antitumor immunity by 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.

Keywords

Immunotherapy; MiR-195; Nanobubbles; Sonodynamic therapy; Ultrasound.

Figures
Products
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  • HY-D0938
    99.01%, Cell Proliferation Fluorescent Probe