以过表达CXCR4 的间充质干细胞为载体的骨肉瘤纳米磁流体靶向热疗

项目名称： 以过表达CXCR4 的间充质干细胞为载体的骨肉瘤纳米磁流体靶向热疗

项目编号： No.81472511

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 边振宇

作者单位： 南京医科大学

项目金额： 72万元

中文摘要： 骨肉瘤是青少年最常见的原发恶性骨肿瘤，转移病灶的出现是骨肉瘤治疗失败以及低生存率的主要原因。磁流体热疗(MFH) 是将纳米技术和热疗技术相结合的一种新兴热疗方法，在肿瘤治疗领域具有较大的应用前景。申请人既往的研究表明间充质干细胞(MSCs)对骨肉瘤及其转移灶具有靶向性，其表达的趋化因子受体4（CXCR4）可与肿瘤细胞分泌的基质细胞衍生因子-1（SDF-1）结合，介导其迁移。本研究首先探讨CXCR4过表达和超顺磁性氧化铁纳米粒子（SPION）标记对MSC迁移和增殖的影响，分析标记的MSCs对骨肉瘤原发及转移病灶的趋向性。然后利用过表达CXCR4的MSC 对骨肉瘤的靶向性，将SPION 携带至骨肉瘤原发及转移病灶内，再施以外加交变磁场，实现对骨肉瘤原发灶及多发转移病灶的靶向热疗。本疗法有望为骨肉瘤的疗效带来突破。

中文关键词： C18_骨肿瘤；间充质干细胞；趋化因子受体4；纳米磁流体；靶向热疗

英文摘要： Osteosarcoma is the most common malignant bone tumor in children and adolescents. Metastasis is the major cause for therapeutic failure and low survival rate of osteosarcoma. Magnetic fluid hyperthermia (MFH) is a new thermal therapy using nanotechnology and hyperthermia, and it is promising in treating malignant cancers. Previous studies performed by the applicant revealed that mesenchymal stem cells (MSCs) can target to osteosarcoma and its metastases. The chemokine receptors type 4(CXCR4) expressed by MSCs can bind to stromal cell-derived factor-1 (SDF-1) secreted by osteosarcoma cells, which will mediate migration of MSCs. This study will first investigate the influence of CXCR4 overexpression and superparamagnetic iron oxide nanoparticles (SPION) labeling on migration and proliferation of MSCs, and analyze targeting ability of labeled MSCs towards primary osteosarcoma and metastatic lesions. Then MSCs over-expressing CXCR4 will be used as vehicles carrying SPION to primary osteosarcoma and metastatic lesions, then external alternating magnetic field will be introduced to conduct targeted MFH for primary osteosarcoma and multiple metastatic lesions. The study will bring breakthrough to the therapy of osteosarcoma.

英文关键词： bone tumor;mesenchymal stem cell(MSC);Chemokine receptor type 4(CXCR4);nano-magnetic fluid;targeted hyperthermia