Hepatocellular carcinoma (HCC) is one of the most common malignancies imposing a serious threat to human health worldwide. To date, the effect of HCC chemotherapy has been limited due to drug resistance. Combination therapy of chemotherapeutic drugs and siRNA represents an emerging strategy that may improve anticancer effects by synergistic actions. The current study was aimed at achieving better HCC treatment via combination therapy, in which PEI-modified liposomes prepared by a thin-film hydration method were used to codeliver sorafenib (SF) and siRNA targeting GPC3 gene (siGPC3). Under optimized experimental conditions, SF and siGPC3 were effectively loaded into liposomes (SF-PL/siGPC3). SF-PL/siGPC3 with selected sizes and zeta potentials effectively accumulated at tumor sites and entered HCC cells. The two codelivered therapeutic agents exerted good anticancer effects by jointly suppressing the expression of the anti-apoptotic GPC3 gene and the proliferative cyclin D1 gene in HCC. Consequently, the intravenous injection of SF-PL/siGPC3 into nude mice bearing subcutaneous human HepG2 xenografts effectively inhibited tumor growth and also increased the survival rates of animals. These results revealed the great potential of the PEI-modified liposomal nanomedicine carrying SF and siGPC3 to improve HCC treatment.

中文翻译：

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索拉非尼和GPC3 s​​iRNA与PEI修饰的脂质体的代码传递用于肝癌治疗

肝细胞癌（HCC）是最普遍的恶性肿瘤之一，对全世界的人类健康构成了严重威胁。迄今为止，由于耐药性，HCC化学疗法的作用受到限制。化疗药物和siRNA的联合治疗代表了一种新兴的策略，可以通过协同作用改善抗癌作用。当前的研究旨在通过以下途径获得更好的HCC治疗联合疗法，其中通过薄膜水化方法制备的PEI修饰的脂质体用于编码肝索拉非尼（SF）和靶向GPC3基因的siRNA（siGPC3）。在优化的实验条件下，将SF和siGPC3有效地加载到脂质体（SF-PL / siGPC3）中。具有选定大小和ζ电位的SF-PL / siGPC3有效地聚集在肿瘤部位并进入了HCC细胞。通过共同抑制抗凋亡的GPC3基因和增殖性细胞周期蛋白D1基因在肝癌中的表达，两种编码递送的治疗剂发挥了良好的抗癌作用。因此，向携带皮下人HepG2异种移植物的裸鼠静脉内注射SF-PL / siGPC3有效抑制了肿瘤的生长，并且还提高了动物的存活率。