超声破坏LHRH-紫杉醇脂质微泡靶向治疗卵巢癌及机制研究

项目名称： 超声破坏LHRH-紫杉醇脂质微泡靶向治疗卵巢癌及机制研究

项目编号： No.30801228

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 化学工业

项目作者： 常淑芳

作者单位： 重庆医科大学

项目金额： 20万元

中文摘要： 卵巢癌是最常见的妇科三大恶性肿瘤之一，由于起其病隐匿，早期诊断困难，死亡率居妇科三大恶性肿瘤之首位。化疗是卵巢癌的重要辅助治疗手段，但化疗药物的非靶向杀伤限制了其临床应用。以超声造影剂为载体携带药物靶向传输技术是一种新型、无创的肿瘤治疗技术，它既可促进药物进入细胞内，又能提高药物治疗的靶向性，减少全身副反应。本课题以卵巢癌细胞特异性LHRH受体为靶点，分别采用共价结合及生物素-亲和素桥接法构建了LHRHa靶向脂质微泡及LHRHa靶向载紫杉醇脂质微泡。该微泡体外可特异性与表达LHRH受体的卵巢癌细胞株Ovcar3及A2780/DDP结合，体内通过荷瘤鼠腹腔注射及尾静脉注射，可与肿瘤组织特异性结合，增强显影效果。超声体内外激发该靶向微泡可引起药物定向释放，并增加肿瘤细胞膜的通透性，从而增强肿瘤细胞对化疗药物的摄取，提高化疗药物顺铂及紫杉醇的靶向杀伤及凋亡诱导作用，延长了荷瘤裸鼠的存活时间。该课题所合成的LHRHa靶向声学造影剂在国内外尚未见报道，对卵巢癌的早期诊断及靶向治疗方面将具有重要的临床价值。

中文关键词： 卵巢癌；超声；紫杉醇；脂质微泡；靶向治疗

英文摘要： Ovarian cancer is one of the most common gynecological malignancy, it is most often develops asymptomatically and early diagnosis is difficult.The mortality rate of ovarian cancer ranks first in gynecological cancer.Chemotherapy is an important adjuvant treatment for ovarian cancer,but the untargeted killing of chemotherapy limits its clinical application.Ultrasound-targeted microbubbles destruction (UTMD) technology is a promising approach for cancer treatment,which can stimulate cell membrane permeability and increase the uptake of drug and improve the drug efficiency and reduce the side effects.In the present study,we have constructed LHRHa targeted lipid microbubbles and paclitaxel loaded LHRHa targeted lipid microbubbles by covalently bound and biotin-avidin bridge method.The microbubbles can bound to the surface of ovarian cancer cell lines Ovcar3 and A2780/DDP specifically in vitro and enhance tumor ultrasound echo in vivo. Ultrasound can stimulate the targeted microbubbles drugs release and increase the membrane permeability of ovarian cancer cell, thereby enhancing tumor cell uptake of paclitaxel and cisplatin,which improved the drug targeting killing efficiency and prolonged the survival time of nude mice.To the best of the present authors' kownledge,LHRHa targeted lipid microbubble have not yet reported elsewhere.It might become a promising strategy for early diagnosis and targeted therapy of ovarian cancer.

英文关键词： ovarian cancer;ultrasound;paclitaxel; lipid microbubbles;targeted therapy