HER2靶向新型纳米载体荷载BCRP-siRNA经UTMD逆转乳腺癌耐药性的实验研究

项目名称： HER2靶向新型纳米载体荷载BCRP-siRNA经UTMD逆转乳腺癌耐药性的实验研究

项目编号： No.81201097

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 白敏

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 乳腺癌细胞耐药性的产生是化疗失败的主要原因，目前尚缺乏有效手段逆转。最近的研究发现，乳腺癌耐药蛋白(BCRP)的表达与乳腺癌细胞耐药性直接相关，提示采用RNAi阻断BCRP的表达有望逆转乳腺癌耐药细胞的耐药性、改善预后。使用何种手段导入目的基因直接决定治疗效果。目前绝大多数导入方法不同程度存在低效、副作用大、表达时间短的缺陷。我们的前期研究发现，超声靶向破坏微泡(UTMD)具有靶向辐照定向转染、安全高效的优势，并成功构建了载siRNA的新型纳米递送系统，预实验已证实UTMD能促进乳腺癌耐药细胞对载siRNA纳米粒的摄取。本项目将在此基础上，针对HER2阳性乳腺癌，制备携抗HER2的mPEG-PLGA-PLL，包裹BCRP-siRNA，通过UTMD作用使复合载体穿过血管壁，靶向HER2阳性乳腺癌细胞，沉默BCRP。这种"多重靶向"新技术有望实现安全、高效、长期稳定逆转乳腺癌耐药性的目的。

中文关键词： 超声；微泡；乳腺癌；耐药；纳米

英文摘要： Drug resistance of breast cancer is one of the most causes of failure in clinical chemotherapy. Currently there is no effiective means to reverse it. Recent researches show the expression of breast cancer resistance protein (BCRP) gene is directly related to breast cancer cell's drug resistance. RNA interference (RNAi) is suggested to be used to block BCRP gene expression, which could help to reverse breast cancer's drug resistance and improve prognosis. what kind of method of transfering target gene is a determining factor to the result of treatment. More or less, most of the methods of transfering target gene have shortcomings of low efficiency, having side effects and short period of expression. Our previous study have found that ultrasound targeted microbubbles destruction (UTMD) has advantages of targeted transfection, security and high efficiency. Meanwhile, we have successfully set up a new nano delivery system that carries siRNA. Preliminary experiment has proven UTMD can facilitate the uptake of loaded siRNA nanoparticles (NPs) by resistant cell of breast cancer. On this basis, our study will aim at HER2-positive breast cancer, prepare mPEG-PLGA-PLL NPs carrying anti-HER2 and encapsulate BCRP-siRNA. Through UTMD, the composite carrier can go through blood vessel and target HER2-positive breast cancer ce

英文关键词： Ultrasound；microbubbles；breast cancer；drug resistance；nanoparticles