Abstract
MicroRNA (miRNA) imaging has been employed to distinguish cancer cells from normal cells by exploiting the overexpression of miRNA in cancer. Inspired by the acidic extracellular tumor microenvironment, we designed a pH-activated DNA nanomachine to enable the specific detection of cancer cells using miRNA imaging. The DNA nanomachine was engineered by assembling two hairpins (Y1 and Y2) onto the surface of a ZIF-8 metal-organic framework (MOF), which decomposed under acidic conditions to release the adsorbed DNA hairpin molecules in situ. The released hairpins were captured by the target miRNA-21 and underwent catalytic hairpin assembly amplification between Y1 and Y2. The detection limit for miRNA assays using the DNA nanomachine was determined to be 27 pM, which is low enough for sensitive detection in living cells. Living cell imaging of miRNA-21 further corroborated the application of the DNA nanomachine in the identification of cancer cell.
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Funding
This work was supported by the National Natural Science Foundation of China (No. 21775132), the National Natural Science Foundation of Hunan province (2022JJ30557), and the Hunan 2011 Collaborative Innovation Center of Chemical Engineering & Technology with Environmental Benignity and Effective Resource Utilization, the project of innovation team of the ministry of education (IRT_17R90).
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Shufen Yao, Xiaojia Zhao, Lingyun Wang, Feng Chen, and Chunyan Chen performed the experiments and revised the manuscript. Hang Gong and Changqun Cai supervised all research. Changqun Cai also wrote the manuscript. All authors contributed to reagents/materials/technical support to this study.
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Supplementary Information
Electronic Supplementary Information (ESI) available: experimental section (Detailed information on the reagents, materials, and apparatus), The sequences of the HPLC-purified oligonucleotide are listed in Table S1. Scanning electron microscopy (SEM) imaging, Nitrogen adsorption-desorption isotherm and Thermogravimetric (TG) characterization of the prepared nanoparticles. Optimization experiment of the probe ratio and conditions. Experiment of actual sample analysis in Table S2. Comparison of several different strategies for intracellular RNA detection using ZIF-8 material in Table S3. See https://doi.org/10.1039/x0xx00000x.
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Yao, S., Zhao, X., Wang, L. et al. pH-activated DNA nanomachine for miRNA-21 imaging to accurately identify cancer cell. Microchim Acta 189, 266 (2022). https://doi.org/10.1007/s00604-022-05340-3
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DOI: https://doi.org/10.1007/s00604-022-05340-3