靶向载药液-气相变氟碳纳米粒研制及其超声分子显像与治疗研究

鉴于超声微泡的几个严重缺陷：①微泡粒径较大，不能穿过血管内皮间隙，靶向能力受到严重制约；②微泡稳定性不够，体内循环时间短；③制备方法上存在缺陷，产率低或具抗原性；④微泡其作为药物或基因载体，有效负载量低，给超声分子显像与治疗研究带来极大困难。本课题基于重要前期研究基础，通过已成熟掌握的薄膜水化法、高速分散均质法、声振法、薄膜挤压及高压均质法等技术手段，采用磷脂成膜材料、针对肿瘤细胞表面成熟靶点叶酸配体、相变型液态氟碳及活性强而治疗剂量低的广谱抗肿瘤药物10-羟基喜树碱，研制一种靶向肿瘤细胞的液-气相变载药氟碳纳米粒即超声分子探针，并联合低强度聚焦超声及诊断超声在多种肿瘤模型上研究其靶向显影及治疗效果，以解决目前超声分子显像与治疗中的核心问题。

Ultrasound molecular imaging and targeted therapy have bee seriously limited by microbubbles for their defects. Firstly, the large size gives low penetrability. Consequently, microbubbles can't pass through the endothelial gap of tumor vessels which restricts their targeting efficiency. Secondly, microbubbles demonstrate poor stability and short circulation time. Thirdly, the preparation methods of microbubbles have some problems with low productivity and antigenicity. Lastly, micobubbles suffer from poor drug/gene loading ability for targeted therapy in combination with ultrasound. The development of appropriate probes is critical to the technologies of ultrasound molecular imaging and therapy. In this project, we will work together to develop the folate receptor targeted, 10-HCPT loaded perfluorocarbon nanoparticles that can generate phase transition with the application of low intensity focus ultrasound and so as to be used for ultrasound molecular imaging and therapy. The targeted imaging and therapy effect will be studied in-vitro and vivo various tumor models. We aim to resolve the essential problems in ultrasound molecular imaging and therapy technology and provide a new means and method for tumor diagnosis and treatment.