Zhang Juan, He Mengyun, Nie Cunpeng, He Manman, Pan Qingshan, Liu Chang, Hu Yanlei, Chen Tingting, Chu Xia
State Key Laboratory of Chemo/Bio-Sensing and Chemometrics , College of Chemistry and Chemical Engineering , Hunan University , Changsha 410082 , P. R. China . Email:
Chem Sci. 2020 Jun 16;11(27):7092-7101. doi: 10.1039/d0sc00339e. eCollection 2020 Jul 21.
Sensitive tumor imaging and precise tumor therapy play critical roles in the cancer combat. Herein, we build a DNA machine based on a primer exchange reaction (PER) for mRNA imaging and gene therapy. By using zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to co-deliver the components including a primer, hairpin and strand displacing polymerase to the living cells, the PER-based DNA machine can be initiated by intracellular survivin mRNA and continuously produce Bcl-2 antisense DNA (ASD), which enables the DNA machine not only to image survivin mRNA but also to implement gene therapy. The results demonstrate that ZIF-8 NPs can protect the polymerases and nucleic acid probes from protease attack and nuclease degradation. After internalization, pH-responsive ZIF-8 NPs can efficiently release cargos from endo-lysosomes due to the protonation effect. The intracellular PER-based DNA machine has been demonstrated to be able to sensitively image survivin mRNA expression levels and selectively kill the cancer cells and has no effect on the normal cells. The PER-based DNA machine may provide a promising platform for early stage tumor diagnosis and more precise tumor therapy.
灵敏的肿瘤成像和精确的肿瘤治疗在抗癌斗争中发挥着关键作用。在此,我们构建了一种基于引物交换反应(PER)的DNA机器,用于mRNA成像和基因治疗。通过使用沸石咪唑酯骨架-8纳米颗粒(ZIF-8 NPs)将包括引物、发夹和链置换聚合酶在内的组件共同递送至活细胞,基于PER的DNA机器可由细胞内生存素mRNA启动,并持续产生Bcl-2反义DNA(ASD),这使得该DNA机器不仅能够对生存素mRNA进行成像,还能够实施基因治疗。结果表明,ZIF-8 NPs可以保护聚合酶和核酸探针免受蛋白酶攻击和核酸酶降解。内化后,pH响应性ZIF-8 NPs由于质子化效应能够有效地从内溶酶体中释放货物。已证明细胞内基于PER的DNA机器能够灵敏地成像生存素mRNA表达水平,并选择性地杀死癌细胞,而对正常细胞没有影响。基于PER的DNA机器可能为早期肿瘤诊断和更精确的肿瘤治疗提供一个有前景的平台。