【摘要】 在多种实体瘤中,let-7a都被证明呈下调状态,而这也与癌症病人的预后情况有直接相关性。通过上调let-7a在癌细胞中的表达,对于研究有效的癌症治疗方案有积极的推动作用。设计了一种负载着荧光素（FAM）修饰的let-7a（FAM-let-7a）的二氧化锰纳米探针,其中FAM的荧光能够被二氧化锰纳米片（MnO₂ NSs）有效淬灭。待探针以胞吞的形式进入肿瘤细胞后,呈高表达状态的谷胱甘肽（GSH）会将MnO₂ NSs降解成锰离子(Mn²⁺),使得负载的FAM-let-7a被释放出来,之前被淬灭的FAM荧光信号重新恢复,利用激光共聚焦荧光显微镜可以实现对细胞内这一过程的原位可视化监测,并对运送到细胞内的FAM-let-7a进行荧光成像。结果表明,MnO₂ NSs作为一种有效的microRNA载体,能够将let-7a模拟物输送进癌细胞,从而上调let-7a的表达,有效诱导其凋亡。更多还原

【Abstract】 Let-7a has been shown to be down-regulated in a variety of solid tumors,and this is directly related to the prognosis of cancer patients.By up-regulating the expression of let-7a in cancer cells,it can promote the research of effective cancer treatment.A manganese dioxide nanoprobe loaded with fluorescein（FAM） modified Let-7a（FAM-let-7a） was designed,in which the fluorescence of FAM could be effectively quenched by manganese dioxide nanosheets（MnO₂ NSs）.After entering tumor cells by endocytosis,MnO₂ NSs will be degraded into manganese ion(Mn²⁺) by the overexpressed glutathione（GSH）.At the same time,the loaded FAM-let-7a will be released and the fluorescence of FAM will be resumed.All of these process can be monitored in situ visually by the use of laser confocal fluorescence microscopy,and the intracellular FAM-let-7a can be imaged fluorescently.The results showed that MnO₂ NSs,as an effective microRNA vector,could deliver let-7a analog into cancer cells,thus up-regulating let-7a expression and effectively inducing the apoptosis of cancer cells.更多还原