RNA-Seq Explores the Mechanism of Oxygen-Boosted Sonodynamic Therapy Based on All-in-One Nanobubbles to Enhance Ferroptosis for the Treatment of HCC

• DOI: 10.2147/ijn.s343361
• Publication Date: 2022-01-06T13:50:10Z
• Authors: Yichi Chen; Haitao Shang; Chunyue Wang; Jiaqi Zeng; Shentao Zhang; Bolin Wu; Wen Cheng
• Keywords: Sonodynamic therapy; Indocyanine Green

Background: The combination of sonodynamic therapy and oxygenation strategy is widely used in cancer treatment. However, due to the complexity, heterogeneity irreversible hypoxic environment produced by hepatocellular carcinoma (HCC) tissues, oxygen-enhancing (SDT) has failed achieve desired results. With emergence ferroptosis with reactive oxygen species (ROS) cytotoxicity, this novel cell death method attracted widespread attention. Methods: In study, nanobubbles (NBs) were connected sonosensitizer Indocyanine green (ICG) construct a 2-in-1 nanoplatform loaded RAS-selective lethal (RSL3, promoter) ( [email protected] NBs), combined oxygen-enhanced SDT potent ferroptosis. addition, low-frequency ultrasound (LFUS) are called ultrasound-targeted nanobubble destruction (UTND) ensure specific drug release improve safety. Results: MDA/GSH other related experimental results show that NBs can enhance Through RNA sequencing (RNA-seq), differential expression LncRNA mRNA before after synergistic treatment was identified, then GO KEGG pathways enrich analyze target genes sensitivity. We found they significantly enriched ferroptosis-related pathway MAPK cascade proliferation. Then, we searched for differentially expressed TCGA Hepatocellular cohort. At same time, evaluated proportion immune infiltration identification co-expression network modules prognostic analysis. it tumor microenvironment carcinoma. risk “SLC37A2” “ITGB7” may represent new ferroptosis-inducing markers have guiding significance treating Conclusion: therapeutic effect vitro been proven be significant, revealing prospect HCC. Keywords: ferroptosis, therapy, HCC, RSL3,