Sorafenib-Doxorubicin脂质体对超声引导下肝癌射频消融治疗效果影响及机制的研究

Ultrasound-guided radiofrequency ablation (RFA) is becoming an important method for conquering hepatocellular carcinoma. But it is difficult for RFA to completely ablate the tumor, and the local recurrence rate is very high. How to reduce the local recurrence rate and increase the scope of ablation are becoming the focus of tumor research. Chemotherapy drug Doxorubicin and molecular targeting drug Sorafenib could increase the treatment area of RFA, meanwhile when these two drugs are combined, we can get synergistic effect, even though, the overall toxic side effect is serious. Liposome technology can solve the problem for its popular targeted drug delivery system. Our research group had successfully established the liposomal Doxorubicin previously, and had verified its anti-tumor effect. The research was based on the establishment of liposomal Sorafenib-Doxorubicin, and evaluated its advantage in decreasing overall toxic side effect. Meanwhile, we combined it with RFA to explore its effect and mechanism on enhancing cells apoptosis, increasing RFA treatment scope, augmenting drug concentration gathering in tumor location, reducing local recurrence rate. In our research we combine RFA, chemotherapy and molecular targeting treatment to increase RFA treatment scope and decrease recurrence rate after RFA, which can provide us with new thinking and method for the clinic comprehensive treatment of hepatocelluar carcinoma.

超声引导下射频消融（RFA）已成为肝癌重要治疗方法。但RFA治疗肿瘤往往难以达到完全消融，局部复发率较高。因此，降低局部复发率及增加消融范围成为研究热点。化疗药Doxorubicin（阿霉素）及分子靶向药物Sorafenib可增加RFA的消融范围，且两药联合应用具有协同作用，但该两者全身毒副反应较大。脂质体技术是目前热门的靶向给药技术。申请人所在课题组前期已成功制备Doxorubicin脂质体并验证了Doxorubicin脂质体抗肿瘤效果。本研究拟通过构建Sorafenib-Doxorubicin脂质体，评价其降低药物毒副反应的优点，将其与RFA联合应用，研究其促进肝癌细胞凋亡，增加射频消融范围，且增加药物在肿瘤部位聚集，降低局部复发率的作用及机制。本研究将RFA、化疗、分子靶向治疗联合起来，以期增加射频消融范围，降低肝癌RFA后复发率，从而为肝癌的临床综合治疗提供新的思路和方法。

射频消融（RFA）治疗肿瘤往往难以达到完全消融，且局部复发率较高。化疗药Doxorubicin及分子靶向药物Sorafenib可增加RFA的消融范围，且两药联合应用具有协同作用。本研究采用薄膜水化法成功构建了Sorafenib-Doxorubicin脂质体，并对其进行基本特征表征，载药包封率测定。通过体内外实验观察脂质体在体内外都有明显的超声造影效果，脂质体在超声转染仪作用下具有液气相转变能力。 通过体外超声显像及透射电镜观察, 验证脂质体在超声转染仪作用下可产生空化效应。建立肝癌裸鼠模型，验证了其可促进肝癌细胞凋亡，增加射频消融范围，并增加药物在肿瘤部位聚集，降低局部复发率。通过本研究，有望将射频消融、化疗及分子靶向治疗联合起来，从而为肝癌的临床综合治疗提供新的思路和方法。