A combined miR-34a and arsenic trioxide nanodrug delivery system for synergistic inhibition of HCC progression after microwave ablation

Abstract

Abstract Background Microwave ablation (MWA) has become an alternative treatment for unresectable hepatocellular carcinoma (HCC), but it does not eliminate the risk of recurrence and metastasis after treatment. Recent studies have demonstrated that miR-34a presents decreased gene expression in residual tumours after ablation therapy and can increase the therapeutic effect of arsenic trioxide against HCC, which brings new opportunities for HCC treatment. Methods A pH-sensitive charge inversion material was used to construct a nanotargeted delivery system based on the synergistic effects of miR-34a and As2O3. We established in vitro and in vivo models of HCC microwave ablation and performed in-depth research on the dual-drug system to inhibit the rapid progression and induce pyroptosis in HCC cells after microwave ablation. Results The antitumour effects were enhanced with the dual-drug nanoparticles relative to the single-drug formulations, and the therapeutic efficacy of the nanoparticles was more significant in a weakly acidic environment. The dual-drug nanoparticles increased the N-terminal portion of GSDME and decreased the expression of Cyt-c and c-met. Conclusions Dual-drug nanoparticles may improve the therapeutic efficacy of HCC treatment after insufficient ablation through Cyt-c and GSDME-N and decrease the expression levels of c-met. These nanoparticles are expected to provide new treatment methods for residual HCC after MWA, prolong the survival of patients and improve their quality of life.

Keywords

• Hepatocellular carcinoma
• Microwave ablation
• Nanodrug delivery
• Arsenic trioxide
• miR-34a