新型可X光显影的体温响应智能水凝胶栓塞材料的构建及其在肝癌经肝动脉化疗栓塞中的应用基础研究

Liver cancer is one of the most common malignant diseases in human. Transcatheter arterial chemoembolization (TACE) is a standard treatment for most terminal-stage patients with liver cancer. However, the long-term curative effect of TACE is dissatisfactory because of the recurrence and metastasis after the operation.The lack of ideal vascular embolization materials and postoperative angiogenesis of the tumor are two important factors that affect the long-term efficacy of TACE. This project aim to design a novel X-ray imaging thermo-sensitive intelligent hydrogel as embolic material to overcome the shortcomings of current clinical commonly used embolic agents. Then, chemotherapeutic drug and angiogenesis inhibitor will been loaded in this radiopaque thermo-sensitive hydrogel to make a novel composite system for the treatment of liver cancer. The complex system can be injected to the tumor blood vessels at all levels through the catheter under the guidance of CT, and then translate into hydrogel in situ in response to the body temperature, serving as a complete and lasting vascular embolization along with sustained release of drugs in tumor site. The drugs loaded thermo-sensitive hydrogel system combined multiple therapies together, such as tumor targeting, arterial embolization, chemotherapy, vascular inhibition and imaging. We expect to improve the efficiency of TACE through the accurate and effective embolism of tumorous artery, locally chemotherapy and long-acting of angiogenesis inhibitor. And a prevention of tumor recurrence and metastasis and reduction of side effects were desired to be achieved at the same time. This study will provide new ideas and theoretical basis for the development of new vascular embolization materials and effective treatment of hepatocellular carcinoma.

肝癌是一种高发病率、高死亡率的恶性疾病。经肝动脉化疗栓塞术（TACE）是大部分中晚期肝癌患者的标准治疗方案，但其术后易复发和转移，中远期疗效欠佳。理想的血管栓塞剂的缺乏和病灶血管术后再生是影响TACE治疗中远期疗效的重要因素。本项目针对目前临床常用栓塞剂的不足之处，拟设计一种新型的可X光显影的体温响应智能水凝胶栓塞材料，构建化疗药物和血管生成抑制剂共负载的水凝胶复合体系。该复合体系可在CT引导下顺利通过微导管到达肿瘤各级血管，然后在体温作用下快速原位凝胶化，形成彻底、持久的血管栓塞，并在肿瘤部位持续释放药物。该方案集“靶向-栓塞-化疗-血管抑制-成像”为一体，通过肿瘤供血动脉的精准有效栓塞、化疗药物在病灶的缓释和血管抑制剂的局部长效作用，实现多种治疗方法联合，有望提高 TACE治疗效果，预防肿瘤复发与转移，减小毒副作用。本项目将为新型血管栓塞材料的开发和肝癌的有效治疗提供新思路与理论依据。

癌症是严重威胁人类健康的重大疾病，目前仍然缺乏有效的治疗手段。本项目以发病率、死亡率高的肝癌为切入点，基于可注射温度敏感水凝胶（PLEL）材料，构建了两种新型的药物递送体系，分别用于肝癌的经肝动脉栓塞化疗（TACE）和肝癌的间质化疗。在此研究基础之上，又开展了一些延展性研究工作，构建了基于温敏水凝胶的递送体系用于恶性实体瘤的局部联合化疗和免疫治疗。取得了阶段性研究成果，在Advanced Functional Materials, Nano Research, Applied Materials Today等本领域国际重要学术刊物上发表论文。为肝癌、胰腺癌等恶性实体瘤的治疗提供了新的思路和理论依据。