肝细胞癌在我国发病率高，目前的治疗手段效果有限，研究提示miRNA表达失调与其发生发展密切相关，调控靶miRNA水平可能是肝癌治疗值得探讨的新领域。在我们前期通过病毒样颗粒递送miR122对肝细胞癌有良好治疗效果的基础上，本研究拟从同时上调miR122和下调miR224两个方面，采用原核表达、噬菌体展示等技术制备表面展示肝癌细胞特异性穿透肽、同时内含pre-miR122-miR224 sponge-pre-miR122序列的重组病毒样颗粒，通过体外、体内实验在细胞和动物水平验证其肝癌抑制作用，并与只含miR122前体或miR224海绵体的效果进行比较，以期为肝癌治疗提供新思路；此外，我们在对肝癌小鼠模型给药治疗时，同时监测肿瘤组织、血清中两种miRNA水平和肿瘤大小变化，分析二者相关性以调整治疗方案，探讨miRNA水平是否可作为上述特异靶向病毒样颗粒使用的伴随检测标志物，提高治疗精准性。

The incidence of hepatocellular carcinoma (HCC) is high in China, and the effect of current treatment is limited. Studies have highlighted that dysregulated microRNA (miRNA) in the tissue of HCC play critical roles in HCC progression, and regulating target miRNA may be a new field worth studying on HCC treatment. Based on the positive results on HCC by delivering miRNA122 with MS2 virus-like particles (VLPs) in our previous work, in this research, we decide to upregulate miRNA122 and downregulate miRNA224 simultaneously using the methods such as prokaryotic expression and phage surface display to prepare VLPs packaging pre-miR122-miR224 sponge-pre-miR122 with HCC specific cell-penetrating peptide on the surface, and then discuss the therapeutic effects in vitro and in vivo as well as on cell and animal level comparing with VLPs only pakaging pre-miRNA122 or miRNA224 sponge in order to provide new idea for the treatment of HCC. Besides, at the time of treatment with VLPs on HCC mouse model, the levels of miR122 and miR224 and tumor size are measured, and the correlations between miRNAs level and tumor size are analyzed to adjust the dosage of VLPs and further to determine whether the level of miRNA could be used as a companion detection biomarker in the targeted therapy using VLPs to improve the accuracy of treatment.