项目名称： 双重靶向肿瘤干细胞的多功能磁性二氧化硅纳米体系的构建及其热化疗干预机制研究

项目编号： No.31500812

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 刘丹丹

作者单位： 河北大学

项目金额： 20万元

中文摘要： 肿瘤干细胞(CSCs) 是维持肿瘤的形成、复发和转移的根源。迄今为止，CSCs生长调控机制尚不清楚，针对CSCs进行肿瘤治疗的特异性靶位也无法确定。因此，CSCs的存在是癌症临床治疗上的重大挑战。可见，研究靶向CSCs的治疗手段、阐明其干预癌症治疗新机制具有重要的科学意义。.随着纳米技术的发展，以纳米颗粒为载体，集热、化疗为一体的综合治疗成为癌症治疗的新趋势。然而，双重靶向CSCs的多功能磁性二氧化硅(SiO2)纳米体系的构建及其热化疗干预机制研究尚未见报导。基于此，本项目将构建一种表面具有CSCs特异性抗体修饰的多功能磁性SiO2纳米载药体系，通过外加磁场实现双重靶向CSCs、集热化疗为一体的治疗方法，深入探讨其热化疗干预CSCs生长调控机制，确定出针对CSCs治疗的靶位。该研究成果将为临床开展靶向CSCs治疗提供基础性研究数据，为探讨肿瘤形成及根治提供新的视角，无疑具有重要的科学意义。

中文关键词： 肿瘤干细胞；多功能磁性纳米颗粒；双重靶向；热化疗联合；调控机理

英文摘要： Cancer stem cells (CSCs) have been shown to play critical role in tumor initiation, relapse, and metastases. So far, the survival mechanisms of CSCs which play a vital role in identifying the target sites remain incompletely understood, resulting in the failure of chemotherapies. Therefore, therapeutic strategies that target and disrupt the survival mechanisms of CSC are the subject of active investigation. With the development of nanotechnology, nanoparticle-based combined thermotherapy and chemotherapy is a new trend of cancer therapy. However, construction of multifunctional magnetic silica nanoparticle for CSCs-dual targeting and the discussion on regulatory mechanism of combined thermotherapy and chemotherapy have not yet been reported. In this project, we propose to develop the multifunctional magnetic core/silica shell nanoparticles to achieve the dual CSCs-targeted delivery and combined thermotherapy and chemotherapy by applying an alternating magnetic field. We will systematically investigate the therapeutic efficacy and possible regulatory mechanism to identify the target sites closely related to CSCs. This deliverables of this project are of great significant for providing a new platform for effective CSCs-targeted cancer therapy and offering novel perspective for the formation and eradication of tumor.

英文关键词： cancer stem cell;multifunctional magnetic nanoparticle;dual-targeting;combined thermotherapy and chemotherapy;regulatory mechanism