Hepatocellular carcinoma (HCC) is one of most common malignancies imposing serious threat to human health worldwide, and thus far the effect of HCC chemotherapy has been limited due to drug resistance. Combinative therapy of chemotherapeutic drugs and siRNA represents an emerging strategy which may improve anticancer effect by synergistic actions. The current study aimed to achieve better HCC treatment via the combinative therapy, in which PEI-modified liposome prepared by thin-film hydration method was used to codeliver Sorafenib (SF) and siRNA targeting GPC3 gene (siGPC3). At optimized experimental conditions, SF and siGPC3 were effectively loaded into the liposome (SF-PL/siGPC3). SF-PL/siGPC3 with selected size and zeta potential accumulated at tumor sites and entered the HCC cells effectively. The two codelivered therapeutic agents exerted good anticancer effect by jointly suppressing the expressions of anti-apoptotic GPC3 gene and proliferative cyclin D1 gene in HCC. Consequently, intravenous injection of SF-PL/siGPC3 into nude mice bearing subcutaneous human HepG2 xenograft inhibited tumor growth and meanwhile increased survival rates of animals effectively. These results revealed the great potential of the PEI-modified liposomal nanomedicine carrying SF and siGPC3 to improve the 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）是对全世界人类健康造成严重威胁的最常见的恶性肿瘤之一，迄今为止，由于耐药性，HCC化疗的作用受到了限制。化疗药物和siRNA的联合治疗代表了一种新兴的策略，可通过协同作用提高抗癌效果。当前的研究旨在通过联合疗法实现更好的HCC治疗，其中通过薄膜水化法制备的PEI修饰脂质体被用于编码Sorafenib（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在肿瘤部位积聚并有效进入HCC细胞。两种共编码的治疗剂通过共同抑制肝癌中抗凋亡的GPC3基因和增殖性细胞周期蛋白D1基因的表达发挥良好的抗癌作用。因此，向携带皮下人HepG2异种移植物的裸鼠静脉注射SF-PL / siGPC3抑制了肿瘤的生长，同时有效地提高了动物的存活率。这些结果揭示了携带SF和siGPC3的PEI修饰的脂质体纳米药物在改善HCC治疗方面的巨大潜力。