共载阿霉素和anti-miR-21寡核苷酸的多功能磁-介孔二氧化硅纳米复合粒子在逆转肿瘤多药耐药方面的研究

项目名称： 共载阿霉素和anti-miR-21寡核苷酸的多功能磁-介孔二氧化硅纳米复合粒子在逆转肿瘤多药耐药方面的研究

项目编号： No.81201804

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 李晶

作者单位： 吉林大学

项目金额： 23万元

中文摘要： 肿瘤化疗药物缺乏靶向性和多药耐药是化疗失败的主要原因。基于anti-miR-21寡聚核苷酸快速、特异性沉默多药耐药相关基因，磁-介孔二氧化硅纳米载体肿瘤靶向性强、载药量高的特点，本项目在前期工作基础上，利用Janus型磁-介孔二氧化硅纳米载体共载化药阿霉素(Dox)和anti-miR-21，制备出集磁靶向、pH响应性和抗多药耐药为一体的多功能组装体（Fe3O4-MSN/Dox-G2/anti-miR-21），并研究其最佳载药和释药参数；整体水平探讨新组装体对肿瘤组织特异性识别、逆转肿瘤多药耐药及治疗作用；细胞水平通过荧光共定位揭示新组装体的细胞内吞、释放和响应机制；分子水平检测Pgp、Bcl-2、PDCD4等耐药基因蛋白表达，阐明组装体逆转多药耐药分子机制。实现化疗药物靶向运输至癌细胞、可控释放的同时，抑制肿瘤多药耐药性，进而提高化疗药物疗效，降低毒副作用，为临床肿瘤综合治疗提供全新方法。

中文关键词： 肿瘤；多药耐药；anti-miR-21；磁-介孔二氧化硅；纳米粒子

英文摘要： The two main causes of chemotherapy failure are absence of tumor targeting and multidrug resistance. Recent studies show that anti-miR-21 oligonucleotide plays a crucial role in reverse tumor multidrug resistance by rapidly and specifically silencing the expression of multidrug-resistance gene. Moreover, Magnetic-mesoporous silica nanocarriers have the characteristics of high medicine carrying and tumor targeting. This project based on our own previous study in successfully synthesis of the novel Fe3O4-SiO2 magnetic-mesoporous Janus particles, and we try to prepare a novel assembly system （Fe3O4-MSN/Dox-G2/anti-miR-21） with co-delivery of the classic cytotoxic drug doxorubicin (Dox) and anti-miR-21 oligonucleotide by magnetic-mesoporous Janus particles. The optimal parameters for loading and releasing drug were explored. In vivo MCF-7/Dox xenograft model was used to detect the effect of the novel assembly system on specific recognition, reversing MDR and inhibiting tumor growth. In vitro, fluorescence imaging was performed to visualize the released Dox and anti-miR-21 to investigate the mechanisms of endocytosis, release and response on in the novel assembly system in MCF-7 human breast cancer cell. Multidrug resistance relative proteins, such as Pgp、Bcl-2 and PDCD4 protein expression were determined to elucidat

英文关键词： tumor；MDR；anti-miR-21；magnetic-mesoporous silica；nanopaticles