基于磁导航和声致相变技术的靶向超声分子探针研制及其多模态显像与治疗研究

Molecular ultrasound technology provides a new efficient means for targeted cancer imaging and therapy. Phase-shift perflurocarbon nanodroplets serve as a novel ultrasound molecular probe, which can overcome the defects of microbubbles for ultrasound molecular imaging and exhibit a great potential to be multimodal contrast agents. However, there have been rare reports focused on the study of phase-shift perflurocarbon nanodroplets in vivo. Moreover, their insufficient tumor-targeting ability leads to poor accumulation in tumor area for further imaging enhancement and local drug release. Based on the preliminary studies of ultrasound molecular imaging and therapy,this programme aims to develop a new type of phase-shift,folate-modified perflurocarbon nanodroplets loaded with antitumor drugs and Fe3O4 nanoparticles, which can serve as a multimodal molecular probe for ultrasound, magnetic resonance and photoacoustic imaging and a vehicle for drug delivery. An ovarian cancer xenograft model would be established to verify the targeting ability of these nanoparticles. The accumulation of the nanoparticles in tumor area will be achieved by dual-targeting techniques, including active ligand-recptor binding and magnetic guidance. The acoustic droplet vaporation (ADV) technology is also applied to ultrasound imaging and drug release. Hence, the multimodal imaging and therapy of ovarian cancer can be eventually achieved, which also provides a new concept and method for cancer molecular imaging and targeted therapy.

超声分子显像与治疗技术为肿瘤靶向显像与精准治疗提供了一种高效的新手段。但超声微泡存在着微径较大、稳定性不够、体内循环时间短、荷载药物/基因量低等缺点。新型液-气相变型氟碳纳米粒联合声致相变技术可望解决上述微泡超声分子显像与治疗研究中存在的问题，纳米粒还具备成为多模态显像剂的巨大潜力。然而，目前相变型氟碳纳米粒体内研究报道较少，且因纳米粒体内肿瘤靶向性不足导致其增强超声显像或靶向释药治疗效果不佳。本课题在前期超声分子显像与治疗研究基础上，拟研制一种携叶酸配体和超顺磁性Fe3O4的相变型载药纳米粒作为可增强超声、磁共振和光声成像的多模态分子探针，并同时作为兼具药物递送作用的多功能显像剂，拟在卵巢癌模型上，通过主动配体-受体结合和磁导航双重靶向诱导技术，提高分子探针在肿瘤部位的靶向性蓄积，并联合声致相变技术，实现对卵巢癌在体多模态分子显像与治疗，为肿瘤分子显像与靶向治疗提供一种新思路与新手段。

超声分子显像与治疗技术为肿瘤靶向显像与精准治疗提供了一种高效的新手段。但超声微泡存在着微径较大、稳定性不够、体内循环时间短、荷载药物/基因量低等缺点。新型液-气相变型氟碳纳米粒联合声致相变技术可望解决上述微泡超声分子显像与治疗研究中存在的问题，纳米粒还具备成为多模态显像剂的巨大潜力。然而，目前相变型氟碳纳米粒体内研究报道较少，且因纳米粒体内肿瘤靶向性不足导致其增强超声显像或靶向释药治疗效果不佳。本课题在前期超声分子显像与治疗研究基础上，拟研制一种携叶酸配体和超顺磁性Fe3O4的相变型载药纳米粒作为可增强超声、磁共振和光声成像的多模态分子探针，并同时作为兼具药物递送作用的多功能显像剂，拟在卵巢癌模型上，通过主动配体-受体结合和磁导航双重靶向诱导技术，提高分子探针在肿瘤部位的靶向性蓄积，并联合声致相变技术，实现对卵巢癌在体多模态分子显像与治疗，为肿瘤分子显像与靶向治疗提供一种新思路与新手段。