共载miR-34a/三氧化二砷纳米递送系统协同抑制肝癌微波消融后残留癌进展的研究

Microwave ablation (MWA) has become one of the alternative treatments for unresectable surgery for hepatocellular carcinoma, but it still faces the risk of recurrence and metastasis after treatment. Recent studies have found that miR-34a gene expression decreases in residual tumor after ablation therapy, and miR-34a can increase the therapeutic effect of arsenic trioxide on HCC, which brings new opportunities for its treatment. Combined with miR-34a can enhance the treatment of HCC by arsenic trioxide. The pH-sensitive charge inversion material mPEG-Dlabile-PAE-DSPE was used to construct a nano-targeted delivery system with synergistic effect of miR-34a and As2O3 and elucidate the in vitro and in vivo transport process of this drug-loaded system. To establish an in vitro and in vivo model of microwave ablation of HCC, and in-depth research of dual drug system on inhibiting HCC rapid progression after microwave ablation in cell pyroptosis, reversal of immunosuppression and autophagy. It is expected to provide a new treatment methods for residual liver cancer after microwave ablation , prolong the survival of patients and improve the quality of life.

微波消融（MWA）是不可切除手术肝细胞癌(HCC) 的替代疗法之一，但仍面临着治疗后复发和转移的风险。近年来研究发现，消融治疗后残留肿瘤miR-34a基因表达下降，而miR-34a能够提高三氧化二砷对HCC的治疗效果，为其治疗带来了新机遇。本课题结合miR-34a能够增敏三氧化二砷对HCC的治疗，采用pH敏感电荷反转材料mPEG-Dlabile-PAE-DSPE构建共载miR-34a/三氧化二砷具有协同作用的纳米靶向递送系统，阐明该类载药系统的体内外转运过程。建立肝癌微波消融的体内外模型，从细胞焦亡、逆转免疫抑制及细胞自噬等方面进行深入研究双药共载系统对肝癌微波消融后残留肿瘤快速进展的抑制作用，有望为肝癌微波消融后残留提供新的治疗方法，延长患者的生存期提高生活质量。

微波消融（MWA）是不可切除手术肝细胞癌(HCC)的替代疗法之一，但仍面临着治疗后复发和转移的风险。近年来研究发现，消融治疗后残留肿瘤miR-34a基因表达下降，而miR-34a能够提高三氧化二砷对HCC的治疗效果，为其治疗带来了新机遇。本课题结合miR-34a能够增敏三氧化二砷对HCC的治疗，采用pH敏感电荷反转材料构建共载miR-34a/三氧化二砷具有协同作用的纳米靶向递送系统，阐明该类载药系统的体内外转运过程。建立肝癌微波消融的体内外模型，从细胞焦亡等方面进行深入研究双药共载系统对肝癌微波消融后残留肿瘤快速进展的抑制作用。双载药纳米粒降低c-met表达水平及提高GSDME-N/GSDME-F比例。较单载药，双载药纳米粒增强抗肿瘤效果，而在弱酸环境下该纳米粒的作用更为显著。