磁性介孔有机氧化硅栓塞微球研制及其在TACE治疗晚期肝癌中的应用研究

Liver cancer is one of the most common malignant tumors in China. Because of the occult of this disease, it’s often at the advanced stage when it is found and cannot be surgically removed. Transcatheter arterial chemoembolization (TACE) is the preferred therapy in the treatment of advanced hepatocellular carcinoma. Embolic agent is most important for TACE treatment. But the embolic agent (including, lipiodol, gelfoam and polyvinyl alcohol microspheres) used for clinical at present commonly exist many shortcomings, such as poor particle uniformity, easy to be cleared, low ability to carry anticancer drug. Thus, they can’t closed tumor blood vessels effectively, neither to kill HCC cells. Mesoporous organosilica is a kind of ideal drug carrier material because of its high surface area, good biocompatibility and high drug loading capacity. But until now, there is no relevant report of the embolization agent based on this mesoporous organsilica material. In this study, we intend to fabricate different sizes of magnetic mesoporous organsilica embolic microspheres, and load anticancer drug-doxorubicin in its mesoporous channel. Then, we monitor the embolism treatment process by magnetic resonance imaging, and evaluate the closed chemotherapy of the organosilica microspheres with different size liver cancer, and the ultimate object of our work is to provide a new way for treatment of advanced hepatocellular carcinoma by TACE.

肝癌是我国常见的恶性肿瘤之一，由于其病症的隐匿性，发现时多处于中晚期，通常无法进行手术切除。经导管动脉化疗栓塞术（TACE）是治疗晚期肝癌的首选疗法。栓塞剂是决定TACE治疗效果的最重要因素，目前临床常用的栓塞剂（包括：碘化油、明胶海绵、聚乙烯醇微球等）存在颗粒均一性差、易被清除、携带抗癌药物能力低等缺点，不能有效的封闭肿瘤血管、杀死肝癌细胞。介孔有机氧化硅具有高的比表面积、良好的生物相容性和稳定性，以及高的药物装载量，是一种理想的药物载体材料。但目前尚未见基于介孔有机氧化硅栓塞剂的相关报道。本研究拟制备不同尺寸的磁性介孔有机氧化硅栓塞微球，并在其孔道内装载抗癌药物阿霉素，通过磁共振成像监控肝癌栓塞治疗过程，评价介孔有机氧化硅栓塞微球对肝癌的封闭化疗效果，为晚期肝癌治疗和疗效评价提供新的途径。

经导管动脉化疗栓塞术（TACE）是治疗晚期肝癌的首选疗法，栓塞剂是决定TACE治疗效果的重要因素。相比于目前临床常用的栓塞剂（碘化油、聚乙烯醇微球等），介孔有机氧化硅是一种理想的药物载体材料。本项目建立了介孔有机氧化硅孔道、骨架和结构调控方法，系统研究了介孔有机氧化硅生物相容性和载药性能。并在此基础上，通过溶胶-凝胶化学方法在磁性微球表面包覆介孔有机氧化硅，成功制备了具有高比表面积和均一尺寸的用于中晚期肝癌TACE治疗的磁性介孔栓塞微球。细胞增殖实验证实制备的磁性介孔栓塞微球具有良好的生物相容性。药物释放曲线表明磁性介孔栓塞微球可实现抗肿瘤药物高效装载和药物在肿瘤酸性条件下的响应性释放。建立兔肝癌模型，并利用磁共振成像技术对磁性介孔栓塞微球进行示踪成像，并对TACE治疗效果进行评估。磁共振成像结果证实载阿霉素的磁性介孔栓塞微球对肝癌的治疗效果显著优于碘油混合阿霉素的治疗效果。本研究为晚期肝癌治疗和疗效评价提供了新的途径。