Ultrasound-activated nano-oxygen sensitizer for sonodynamic–radiotherapy of esophageal cancer†

Background: owing to the intricate nature, variability, and persistent oxygen-deficient environment associated with esophageal cancer (EC) tissues, radiotherapy (RT) sometimes doesn't work as well because some cancer cells can resist the radiation to a certain extent. This can lead to the cancer coming back in the same spot or even making the treatment ineffective. The integration of RT with oxygenation strategies is a common approach in cancer treatment. The advent of oxygen-enhancing sonodynamic therapy (SDT), leveraging the cytotoxic effects of reactive oxygen species (ROS), has garnered significant attention as an innovative approach to inducing cell death. Methods: this study utilized nanobubbles (NBs) containing the acoustic sensitizer indocyanine green (ICG) to create a nanoplatform (ICG@O₂ NBs) that incorporates oxygen-enhanced SDT and RT. Besides, NBs are paired with low-frequency ultrasound (LFUS), known as ultrasound-targeted nano-bubble destruction (UTND), for precise drug release and improved safety. Results: experimental findings, including JC-1/DCFH-DA assays, demonstrate that ICG@O₂ NBs effectively enhance the performance of both RT and SDT. RNA sequencing (RNA-seq) demonstrated differential expression of mRNA and LncRNA prior to and after co-treatment. KEGG and GO pathway analysis were then conducted for enriching and recognizing target genes and pathways correlated with the sensitivity of RT, which were revealed to be remarkably clustered in RT-associated pathways. Conclusion: in vitro and in vivo investigations have indicated significant efficacy of synergistic treatments, highlighting the potential of combining NBs with SDT and RT for managing EC.