Biomineralized metal–organic framework nanoparticles enable a primer exchange reaction-based DNA machine to work in living cells for imaging and gene therapy,Chemical Science

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Biomineralized metal–organic framework nanoparticles enable a primer exchange reaction-based DNA machine to work in living cells for imaging and gene therapy
Chemical Science ( IF 7.6 ) Pub Date : 2020-06-16 , DOI: 10.1039/d0sc00339e
Juan Zhang ₁ , Mengyun He ₁ , Cunpeng Nie ₁ , Manman He ₁ , Qingshan Pan ₁ , Chang Liu ₁ , Yanlei Hu ₁ , Tingting Chen ₁ , Xia Chu ₁

Affiliation

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.

中文翻译：

生物矿化金属有机框架纳米颗粒使基于引物交换反应的 DNA 机器能够在活细胞中工作，用于成像和基因治疗

灵敏的肿瘤成像和精确的肿瘤治疗在癌症斗争中发挥着关键作用。在此，我们构建了基于引物交换反应 (PER) 的 DNA 机器，用于 mRNA 成像和基因治疗。通过使用沸石咪唑框架-8纳米颗粒（ZIF-8 NP）将引物、发夹和链置换聚合酶等成分共同递送至活细胞，基于PER的DNA机器可以由细胞内生存素mRNA启动并连续生产Bcl-2 反义 DNA (ASD)，使 DNA 机器不仅可以对生存素 mRNA 进行成像，还可以实施基因治疗。结果表明，ZIF-8 NP 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，由于质子化效应，pH 响应型 ZIF-8 NP 可以有效地从内溶酶体中释放货物。基于 PER 的细胞内 DNA 机器已被证明能够灵敏地成像生存素 mRNA 表达水平并选择性杀死癌细胞，并且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。

更新日期：2020-07-15

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