超声辐照载药纳米囊泡对宫颈癌靶向治疗及疗效监测的实验研究

Chemotherapy is an indispensable adjunctive method to cervical cancer. As conventional systemic medication often represents low effect and high rate of adverse incident, targeted-chemotherapy has gained great concern for its potential superiority. Usually used as a drug-carrier, ultrasonic microbubble can promote the aggregation of drug in the targeted lesion and enhance therapy effect. Compared with ultrasonic micron- bubble, Nano-microbubble (created by nanotechnology) seems even more suitable for targeted-chemotherapy. Nano-microbubble has very small size, which make it easily to get through vascular endothelial barrier and reach the targeted lesion. Nevertheless, targeting radicals can be easily introduced into the nano-microbubbles to improve their targeting capability. ..We have successfully developed nano-microbubbles using high polymer materials in earlier study. In present project, we plan to introduce ScFv and other specific radicals into the nano-bubbles. Thus these bubbles will possess high targeting ability and can be released by ultrasonic control. Paclitaxel and pentafluorobutanen will be loaded in the bubbles as chemotherapy agents. This specially designed compound will be tested in nude mouse model with cervical cancer and evaluate its effect, efficiency and adverse incidence. If successful, this project will provide a new approach of cervical cancer targeted therapy and monitoring. It is of great significance in improving the chemotherapy effects, reducing the side effects and enhancing the prognosis.

化疗是目前宫颈癌治疗不可或缺的辅助手段，但全身用药副作用大、疗效较差。采用超声微泡为载体有利于药物在病灶区域的聚集，提高治疗的靶向性。而应用纳米技术制备的纳米微泡具有粒径小、容易引入靶向基团及可通过血管内皮细胞屏障等优点，较目前的微米级微泡更易实现靶向治疗。本研究拟在前期已合成高分子材料聚合物纳米微泡的基础上，进一步制备具有高靶向性及超声控释和显像功能的纳米聚合物囊泡，同时负载化疗药紫杉醇及可液/气相变的五氟丁烷，携带抗人宫颈癌单克隆抗体单链片段（ScFv）进一步提高微泡的主动靶向传输，以裸鼠宫颈癌SiHa细胞皮下移植瘤为模型，采用低频超声辐照控制药物释放及吸收，并与气化产生的聚合物微泡协同作用，以达到靶向治疗及显像的双重目的。本研究的成功将为宫颈癌靶向治疗及监测提供一种全新的方法，对于提高宫颈癌化疗效果，降低化疗副作用、改善患者预后具有重要意义。

化疗是宫颈癌治疗不可或缺的辅助手段，但全身用药副作用大，疗效较差。高强度聚焦超声（High Intensity Focused Ultrasound, HIFU）作为一种非侵入的治疗手段，通过热效应及空化效应等使肿瘤细胞凝固性坏死，达到肿瘤治疗作用。应用纳米技术制备的纳米颗粒粒径较小，可通过血管内皮细胞屏障，具有较好的被动靶向作用。本研究成功制备了负载化疗药物多烯紫杉醇及可液／气相变的五氟丁烷的脂质纳米颗粒，联合高强度聚焦超声消融技术，以裸鼠宫颈癌SiHa细胞皮下移植瘤为模型，脂质纳米颗粒通过被动靶向作用可聚集在肿瘤组织，改变靶区组织声学特性，提高HIFU消融效率，同时在HIFU 作用下在肿瘤组织局部释放药物，达到靶向化疗的目的。本研究为宫颈癌靶向治疗及监测提供了一种新的方法，对于提高宫颈癌化疗效果、降低化疗副作用、改善患者预后具有重要意义。