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

Abstract

\n Background\n\nMicrowave ablation (MWA) has become an alternative treatment for unresectable surgery for hepatocellular carcinoma (HCC), but it still faces the risk of recurrence and metastasis after treatment. Recent studies have found that miR-34a presents decreased gene expression in residual tumours after ablation therapy and can increase the therapeutic effect of arsenic trioxide on HCC, which brings new opportunities for its treatment.\nMethods\n\nA pH-sensitive charge inversion material was used to construct a nanotargeted delivery system that presents the synergistic effect of miR-34a and As2O3. We established in vitro and in vivo models of microwave ablation of HCC and performed in-depth research on dual drug systems to inhibit the rapid progression of HCC after microwave ablation in cell pyroptosis.\nResults\n\nThe antitumour effect was enhanced with double-drug nanoparticles relative to a single formulation, and the therapeutic efficacy of the nanoparticles was more significant in a weakly acidic environment. Dual-drug nanoparticles could increase the N-terminal portion of GSDME, decrease the expression of Cyt-c and c-met.\nConclusions\n\nDual-drug nanoparticles may improve the therapeutic efficacy of HCC with insufficient ablation through Cyt-c and GSDME-N and decrease the expression levels of c-met. It is expected to provide new treatment methods for residual liver cancer after microwave ablation, prolong the survival of patients and improve quality of life.