脂质体多聚物混合型纳米颗粒携带FOLFIRINOX有效成分治疗胰腺癌的疗效研究

项目名称： 脂质体多聚物混合型纳米颗粒携带FOLFIRINOX有效成分治疗胰腺癌的疗效研究

项目编号： No.31470957

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 任贺

作者单位： 天津医科大学

项目金额： 90万元

中文摘要： 胰腺癌是最难治的恶性肿瘤之一，五年生存率仅3%。胰腺癌对传统放化疗治疗反应极差，联合化疗FOLFIRINOX方案（5-氟尿嘧啶/亚叶酸钙、奥沙利铂、伊利替康）在胰腺癌治疗上取得了突破性进展，然而该疗法由于存在严重的副反应，特别是在中国人群中限制了其临床应用范围。近年纳米修饰的化疗药物(如白蛋白紫衫醇)在胰腺癌治疗领域取得了突破性进展，我们拟设计双亲性聚合物纳米颗粒外包脂质体集成各种优秀性能，制备混合型药物载体，并通过聚乙二醇（PEG）和精氨酸-苷氨酸-天冬氨酸（RGD）修饰优化其靶向性，包载FOLFIRINOX有效成分减少其毒性并增强药效，进一步利用临床组织标本构建的胰腺癌原位模型，评估其安全性和有效性，进而通过这种脂质体多聚物混合型载体为提高胰腺癌的疗效提供新的治疗策略。

中文关键词： 纳米颗粒；脂质体；联合化疗；胰腺癌

英文摘要： Pancreatic cancer is one of the most difficult cancer to treat,and the 5 year survival rate is 3%. 5-Fluorouracil/Leucovorin combined with Irinotecan and Oxaliplatin (FOLFIRINOX) have been made a breakthrough in the treatment of pancreatic cancer. But the application of this regimen has been limited because of severe side effect. In recent years, nanoparticles-modified chemotherapeutic reagents have demonstrated excellent efficacy in patients with pancreatic cancer such as nab-paclitaxel. In this study, we designed a novel amphiphilic copolymer vehicle (mPEG-PLGA) covered with liposomes, and then optimized the target effect of the vehicle by PEG and RGD. With this vehicles, we carried the effective components of the FOLFIRINOX to decrease the toxicity and increase the efficacy. Furthermore, we have constructed a pancreatic tumor tissue derived xenograft animal model to evaluate the safety and efficacy, thus providing new strategies for the treatment of pancreatic cancer.

英文关键词： Nanoparticles;liposomes;combined chemotherapy;pancreatic cancer