射频消融术（RFA）因其创伤小、疗效显著，已成为肝癌治疗的主要手段之一。然而，术后高复发率成为临床治疗的难题。RFA可杀死肝癌细胞，但同时也可能激活部分癌细胞侵袭转移程序，尤其是接受亚致死温度的肿瘤周边区域的肝癌细胞，可能发生一系列生物学变化，并成为术后复发的根源。缺氧诱导因子/血管内皮生长因子（HIF-1α/VEGF）和上皮间质转化（EMT）在RFA术后肝癌细胞侵袭转移机制中可能起着关键作用。本课题针对上述信号通路中的关键因子VEGF和Snail，在前期成功制备多功能纳米载体的基础上，赋予纳米载体对肝癌细胞的靶向性，利用siRNA技术，靶向传输siRNA到肝癌细胞，协同沉默VEGF、Snail基因，达到拮抗肝癌复发转移的目的；同时在纳米胶束内包埋超顺磁性氧化铁纳米颗粒，实现对基因沉默效果的MR监测。本课题预期结果对阐明RFA术后肝癌复发转移的机制并寻求有效的分子靶向治疗方法具有重要意义。

Radiofrequency ablation (RFA) has been considered as one of the main means for the treatment of hepatocellular carcinoma (HCC) because of its efficacy and relatively less invasion. However, the high HCC recurrence rate after RFA has been a challenge for the clinical treatment. During the RFA procedure, heat ablation not only could kill HCC cells, but also might activate HCC cells invasion and metastasis processes, particularly for those received sublethal heat treatment at the peripheral zone of the tumor. Sublethal heat treatment could skew HCC cells towards a series of biological transformation, which may be the sources of HCC recurrence. Up to now, the mechanism underling the RFA-induced HCC recurrence still remains unexplored. According to the recent researches, hypoxia inducing factor-1α/vascular endothelial growth factor（HIF-1α/VEGF）and epithelial-mesenchymal transition (EMT) may play the key roles for the HCC recurrence. Aiming at VEGF and Snail, the key factors of the HIF-1α/VEGF and EMT signal paths, we want to build a novel nano-carrier targeting HCC cells based on our previous experiences of building multifunctional nano-carriers, which can transfer siRNAs (VEGF siRNA and Snail siRNA) into HCC cells and silence VEGF and Snail genes synergistically, to achieve the goal of antagonizing HCC recurrence and metastasis after RFA. Besides these, super paramagnetic iron oxide nanoparticles (SPION) will be embedded into the nano-carrier for the vivo MR monitoring of the genes silencing effects. The expected results of this study will be of great significance in illuminating the mechanism of RFA-induced HCC recurrence and metastasis, and providing important information for exploring an effective molecular targeted therapy.