Endogenous miRNA-Activated DNA Nanomachine for Intracellular miRNA Imaging and Gene Silencing,Analytical Chemistry

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Endogenous miRNA-Activated DNA Nanomachine for Intracellular miRNA Imaging and Gene Silencing
Analytical Chemistry ( IF 6.7 ) Pub Date : 2021-10-08 , DOI: 10.1021/acs.analchem.1c02907
Lie Li ₁ , Yazhou Ren ₁ , Xiaohong Wen ₁ , Qiuping Guo ₁ , Jie Wang ₁ , Suping Li ₁ , Mei Yang ₁ , Kemin Wang ₁

Affiliation

The development of multifunctional nanoplatforms that integrate both diagnostic and therapeutic functions has always been extremely desirable and challenging in the cancer combat. Here, we report an endogenous miRNA-activated DNA nanomachine (EMDN) in living cells for concurrent sensitive miRNA imaging and activatable gene silencing. EMDN is constructed by interval hybridization of two functional DNA monomers (R/HP and F) to a DNA nanowire generated by hybridization chain reaction. After the target cell-specific transportation of EMDN, intracellular let-7a miRNA initiates the DNA nanomachine by DNA strand displacement cascades, resulting in an amplified fluorescence resonance energy-transfer signal and the release of many free HP sequences. The restoration of HP hairpin structures further activates the split-DNAzyme to identify and cleave the EGR-1 mRNA to realize gene silencing therapy. The proposed EMDN shows efficient cell internalization, good biological stability, rapid reaction kinetics, and the ability to avoid false-positive signals, thus ensuring reliable miRNA imaging in living cells. Meanwhile, the controlled activation of the split-DNAzyme activity regulated by the intracellular specific miRNA may be promising in the precise treatment of cancer. Collectively, this strategy provides a valuable nanoplatform for early clinical diagnosis and activatable gene therapy of tumors.

中文翻译：

用于细胞内 miRNA 成像和基因沉默的内源性 miRNA 激活 DNA 纳米机器

开发兼具诊断和治疗功能的多功能纳米平台在抗癌中一直是非常理想和具有挑战性的。在这里，我们报告了活细胞中的内源性 miRNA 激活的 DNA 纳米机器 (EMDN)，用于同时进行敏感的 miRNA 成像和可激活的基因沉默。EMDN 是通过两个功能性 DNA 单体（R/HP 和 F）与杂交链反应产生的 DNA 纳米线的间隔杂交构建的。在 EMDN 的靶细胞特异性转运后，细胞内的 let-7a miRNA 通过 DNA 链置换级联启动 DNA 纳米机器，导致放大的荧光共振能量转移信号和许多游离 HP 序列的释放。HP 发夹结构的恢复进一步激活了 split-DNAzyme 以识别和切割 EGR-1 mRNA 以实现基因沉默治疗。所提出的 EMDN 显示出有效的细胞内化、良好的生物稳定性、快速的反应动力学以及避免假阳性信号的能力，从而确保了活细胞中可靠的 miRNA 成像。同时，由细胞内特异性miRNA调节的分裂DNA酶活性的受控激活可能在癌症的精确治疗中大有希望。总的来说，该策略为肿瘤的早期临床诊断和可激活的基因治疗提供了一个有价值的纳米平台。从而确保活细胞中可靠的 miRNA 成像。同时，由细胞内特异性miRNA调节的分裂DNA酶活性的受控激活可能在癌症的精确治疗中大有希望。总的来说，该策略为肿瘤的早期临床诊断和可激活的基因治疗提供了一个有价值的纳米平台。从而确保活细胞中可靠的 miRNA 成像。同时，由细胞内特异性miRNA调节的分裂DNA酶活性的受控激活可能在癌症的精确治疗中大有希望。总的来说，该策略为肿瘤的早期临床诊断和可激活的基因治疗提供了一个有价值的纳米平台。

更新日期：2021-10-19

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