Zhang Huairong, Li Binxiao, Sun Zhaomei, Zhou Hong, Zhang Shusheng
Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers , College of Chemistry and Chemical Engineering , Linyi University , Linyi 276005 , P. R. China . Email:
Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong , Shandong Normal University , Jinan 250014 , P. R. China.
Chem Sci. 2017 Dec 1;8(12):8025-8029. doi: 10.1039/c7sc03772d. Epub 2017 Sep 25.
Cancer therapies based on reactive oxygen species (ROS) have emerged as promising clinical treatments. Electrochemiluminescence (ECL) technology has also attracted considerable attention in the field of clinical diagnosis. However, studies about the integration of ECL diagnosis and ROS cancer therapy are very rare. Here we introduce a novel strategy that employs ECL technology and ROS to fill the above vacancy. Briefly, an ITO electrode was electrodeposited with polyluminol-Pt NPs composite films and modified with aptamer DNA to capture HL-60 cancer cells with high specificity. After that, mesoporous silica nanoparticles (MSNs) filled with phorbol 12-myristate 13-acetate (PMA) were closed by the telomerase primer DNA (T-primer DNA) and aptamer. After aptamer on MSN@PMA recognized and combined with the HL-60 cancer cells with high specificity, T-primer DNA on MSN@PMA could be moved away from the MSN@PMA surface after extension by telomerase in the HL-60 cancer cells and PMA was released to induce the production of ROS by the HL-60 cancer cells. After that, the polyluminol-Pt NPs composite films could react with hydrogen peroxide (a major ROS) and generate an ECL signal. Thus the intracellular telomerase activity of the HL-60 cancer cells could be detected . Besides, ROS could induce apoptosis in the HL-60 cancer cells with high efficacy by causing oxidative damage to the lipids, protein, and DNA. Above all, the designed platform could not only detect intracellular telomerase activity instead of that of extracted telomerase, but could also kill targeted tumors by ECL technology and ROS.
基于活性氧(ROS)的癌症治疗方法已成为有前景的临床治疗手段。电化学发光(ECL)技术在临床诊断领域也引起了广泛关注。然而,关于ECL诊断与ROS癌症治疗相结合的研究非常罕见。在此,我们介绍一种采用ECL技术和ROS来填补上述空白的新策略。简而言之,在ITO电极上电沉积聚鲁米诺-Pt纳米颗粒复合膜,并用适配体DNA进行修饰,以高特异性捕获HL-60癌细胞。之后,填充有佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)的介孔二氧化硅纳米颗粒(MSN)被端粒酶引物DNA(T-引物DNA)和适配体封闭。当MSN@PMA上的适配体高特异性地识别并结合HL-60癌细胞后,HL-60癌细胞中的端粒酶将MSN@PMA上的T-引物DNA延伸后从MSN@PMA表面移开,PMA被释放,诱导HL-60癌细胞产生活性氧。之后,聚鲁米诺-Pt纳米颗粒复合膜可与过氧化氢(一种主要的活性氧)反应并产生ECL信号。因此,可以检测HL-60癌细胞的细胞内端粒酶活性。此外,活性氧可通过对脂质、蛋白质和DNA造成氧化损伤,高效诱导HL-60癌细胞凋亡。最重要的是,所设计的平台不仅可以检测细胞内端粒酶活性而非提取的端粒酶活性,还可以通过ECL技术和活性氧杀死靶向肿瘤。