抗脑肿瘤干细胞脂质体的构建及其对脑肿瘤干细胞的调节机制研究

项目名称： 抗脑肿瘤干细胞脂质体的构建及其对脑肿瘤干细胞的调节机制研究

项目编号： No.81460540

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： 应雪

作者单位： 石河子大学

项目金额： 45万元

中文摘要： 科学问题：恶性脑肿瘤病人生存期短，脑肿瘤边界不清、脑结构复杂使手术具有高度风险。脑肿瘤干细胞是导致脑肿瘤复发、转移的主要原因之一，常规化疗药对肿瘤干细胞是无效的。如何使化疗药物在跨越血脑屏障进入到脑室后，靶向浓集于脑肿瘤同时又能诱导脑肿瘤干细胞凋亡是仍待解决的重要科学问题。目的：以替莫唑胺为模型化疗药物、以奎纳克林为凋亡基因调节剂包封于脂质体内，构建的全新的抗脑肿瘤及诱导肿瘤干细胞凋亡的靶向脂质体，可在杀灭耐药肿瘤细胞的同时，根治肿瘤干细胞，从而防止肿瘤干细胞导致的复发与转移。通过（1）抗脑肿瘤及诱导肿瘤干细胞凋亡的靶向脂质体构建；（2）肿瘤干细胞识别、鉴定与MTT研究；（3）调控分子机制研究；（4）在动物肿瘤移植模型中的疗效评价；（5）动物体内的靶向性研究，阐明其效应与机制。研究意义：探索根治难治性肿瘤和肿瘤复发的治疗策略，具有理论探索意义和潜在临床应用价值。

中文关键词： 脂质体；肿瘤靶向；靶向传递；靶向给药系统；脑靶向

英文摘要： Scientific problems: The mean survival time of patients with glioblastoma is only one year. Malignant brain tumor features fast growth, high recurrence rate after surgical operation, and highly invasive ability. Cancer stem cells play a critical role in both disease initiation and relapse of treated brain cancers.The results of literature investigations indicated that how to improve the transport of anticancer drugs across BBB, and how to enhance the drug targeting to brain tumor tissue and brain tumor stem cell still remained to be the major clinical difficult issues, and therefore, to be the unsolved scientific questions. Objectives: A novel kind of targeting anticancer liposomes is prepared by conjugating a ligand onto the liposome surface for enhancing permeability of drug across the BBB, and by simultaneously coupling another ligand onto the same liposome surface for targeting brain tumor, and modifing the agent of inducing apoptosis on cancer stem cells into the same liposome for anti-tumor stem cell in brain. Research contents: (1) To develop a novel kind of targeting liposomes, (2) To assay recognition, appraisement and MTT research on brain tumor stem cell, (3) research on molecular regulation mechanism,(4) To evaluate anti-tumor effects in vivo on C6 animal model, (5) To performe the targeting evaluation of liposomes on animal. Significance: It is theory and clinical significance to explore the therapy strategies on curing refractoriness tumor and relapse of treated cancers.

英文关键词： liposomes;tumor targeting;targeting delivery;targeting drug delivery system;brain targeting