载USPIO/索拉菲尼液态氟碳纳米脂质体动态示踪及治疗肝癌射频消融术后残癌区肿瘤相关巨噬细胞

Researches suggest that TAM is related to the invasion and recurrence of liver cancer, which is the vital target in tumor therapy. In the preliminary research, we found that postoperative residual cancer area of RFA appeared aggregation of TAM. Accordingly, We wonder whether the timing of TAM emerging in the tumor ablation area after RFA is dynamically monitored and visualized, then drug delivery early in visual guided ways that improve the effect of esidual cancer after RFA surgery? We previously synthesized long circulating nanoliposomes with liquid perfluorocarbon. Therefore, we propose to synthesize nanoparticles encapsulated of USPIO and Sorafenib withTAM specific antibodies targeting modification on the basis of the previous study. By using MRI dynamic monitoring TAM localization, further the use of ultrasonic irradiation to perfluorocarbon liquid gas phase transition occurs, ultrasound imaging and drug sentinel release reached. On the cell and animal models, the dynamic tracer TAM development and the therapeutic effect of MRI and ultrasound will observe. The implementation of this project is expected to provide a new method for early dynamic monitoring and treatment of remnant cancer TAM after liver cancer RFA, and provide a new idea for the treatment of residual cancer after RFA.

研究表明肿瘤相关巨噬细胞（TAM）与肝癌侵袭及复发密切相关，是肿瘤治疗的重要靶点。我们前期实验发现肝癌射频消融（RFA）术后残癌区出现TAM聚集。据此，我们设想：如能对RFA术后肿瘤消融区域TAM出现时机进行动态监测、直观显像，早期进行可视化引导给药，是否能有助于提高肝癌RFA术后残癌治疗效果呢？为此，本项目拟在前期已合成的液态氟碳纳米长循环脂质体基础上，同时包载USPIO及索拉菲尼，并进行TAM特异抗体靶向性修饰，制备具有诊疗一体化的多功能纳米分子探针，通过抗体介导的主动靶向，利用MRI动态示踪定位，进一步采用超声辐照使液态氟碳发生液气相变，达到超声显影及药物定点释放。在细胞及动物模型上，观察MRI及超声动态示踪TAM显影及治疗效果。本项目的实施有望为肝癌RFA术后残癌TAM进行早期动态监测及治疗提供新方法，为肝癌RFA术后残癌治疗提供新思路。

研究表明肿瘤相关巨噬细（TAM）与肝癌侵袭及复发密切相关，是肿瘤治疗的靶点。我们前期实验发现肝癌射频消融（RFA）术后残癌区出现TAM聚集。据此，我们设想如果对RFA术后肿瘤消融区域TAM出现时机进行动态监测、直观显像，早期进行可视化引导给药，以期提高肝癌RFA术后残癌治疗效果。本项目拟在前期已合成的液态氟碳纳米长循环脂质体基础上同时包载USPIO及索拉菲尼，并进行TAM特异抗体靶向性修饰，制备具有诊疗一体化的多功能纳米分子探针。 目前已完成对载USPIO纳米载体的物理表征，细胞毒性评估，靶向性验证以及小鼠肝癌模型、消融不全模型的构建。

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