项目名称: 超声破坏LHRH-纳米微泡靶向递送、定位释放紫杉醇治疗卵巢癌的实验研究
项目编号: No.81460394
项目类型: 地区科学基金项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 朱元方
作者单位: 南昌大学
项目金额: 46万元
中文摘要: 卵巢癌死亡率居妇科恶性肿瘤之首,寻求靶向、高效治疗方法是其研究的热点和难点。利用肿瘤特异性靶向微泡造影剂携载药物递送至治疗靶区,声像图监控下超声定时、定位击破载药微泡,于靶区内释放高浓度药物从而实现高效抗癌效应是肿瘤治疗的一种新策略。我们前期成功制备并验证了具有强血管穿透力和靶向结合卵巢癌的LHRH(促黄体生成素释放激素)-纳米微泡。基于该研究基础,本课题拟将高效化疗药物紫杉醇包封于LHRH-纳米微泡中构建载紫杉醇 LHRH-纳米微泡;检测载药微泡理化性质、药物包封率及释放率;筛选对卵巢癌细胞活性无明显影响的超声强度和载药微泡浓度实验参数;体外实验研究超声破坏载药微泡对卵巢癌细胞靶向杀伤效应;裸鼠肿瘤模型上研究载药微泡体内声像图特点、荧光分布及在超声可控击破释放药物后的靶向抗癌效应;分析载药微泡破坏后体内紫杉醇组织分布特点、药代动力学参数,为卵巢癌靶向、高效化疗提供新的思路和手段。
中文关键词: LHRH-微泡;超声;靶向治疗;卵巢癌;紫杉醇
英文摘要: Ovarian cancer is the leading cause of mortality compared with all other gynecological malignancies, which makes it become a hot issue but also a very difficult area to seek for targeted and efficient treatment. A new tactic is used at the present to treat the tumor effectively with the help of tumor specific ultrasound contrast agent which can send drugs to the target area. Then the ultrasound will monitor the appearance of microbubbles in target organs. Meanwhile, the ultrasound could cause microbubbles to rupture so that the drugs of high concentrations could be released locally in target tissues and kill tumor cells. In our previous research, we have successfully prepared LHRH-NM and verified its strong vascular penetration and tumor targeting. Based on the result of previous research, our project is aimed at conducting the following studies, hoping to provide a new idea and approach for target, efficient ovarian cancer chemotherapy : 1. to encapsule paclitaxel in LHRH-NM to produce paclitaxel-carrying LHRH-NM; 2. to detect physicochemical properties, drug entrapment efficiency and drug-loading amount; 3. to screen the experiment parameters recorded in ultrasound intensity and microbubbles concentration which have little effect on cell activity; 4. to investigate in vitro the special lethal effects of ultrasound on ovarian cells by LHRH-nano microbubbles loaded with paclitaxel; 5. to study ultrasonographic features, fluorescence distribution and tumor inhibition rate in tumor-bearing nude mice;6. to analyze in vivo paclitaxel tissue distribution and pharmacokinetic parameters after ultrasound destruction at different time points.
英文关键词: LHRH-microbubble;ultrasound;targeted theraphy;ovarian cancer;paclitaxel