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pH-activated DNA nanomachine for miRNA-21 imaging to accurately identify cancer cell

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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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References

  1. Lin Z, Flemington E-K (2011) MiRNAs in the pathogenesis of oncogenic human viruses. Cancer Letters 305:186–199

    Article  CAS  Google Scholar 

  2. Zhang N et al (2021) The role of miRNAs in colorectal cancer progression and chemoradiotherapy. Biomed Pharmacother 134:111099

    Article  CAS  Google Scholar 

  3. Ma X-L et al (2021) Timmermans, Genome-wide analysis of plant miRNA action clarifies levels of regulatory dynamics across developmental contexts. Genome Res 31:811–822

    Article  Google Scholar 

  4. Wu Y-F et al (2015) Nano metal-organic framework (NMOF)-based strategies for multiplexed microRNA detection in solution and living cancer cells. Nanoscale 7:1753–1759

    Article  CAS  Google Scholar 

  5. Xiang Y-Q et al (2020) Microorganism@UiO-66-NH2 composites for the detection of multiple colorectal cancer-related microRNAs with flow cytometry. Anal Chem 92:12338–12346

    Article  CAS  Google Scholar 

  6. van Tienderen Gilles S et al (2019) Recreating tumour complexity in a dish: Organoid models to study liver cancer cells and their extracellular environment. Cancers 11:1706–1723

    Article  Google Scholar 

  7. Fais S, Marunaka Y (2020) The acidic microenvironment: is it a phenotype of all cancers? A focus on multiple myeloma and some analogies with diabetes mellitus. Cancers 12:3226–3239

    Article  CAS  Google Scholar 

  8. Noguchi F et al (2017) Calcium-dependent enhancement by extracellular acidity of the cytotoxicity of mitochondrial inhibitors against melanoma. Cancers 16:936–948

    CAS  Google Scholar 

  9. Yu J et al (2019) Magnetic reactive oxygen species nanoreactor for switchable magnetic resonance imaging guided cancer therapy based on pH-sensitive Fe5C2@Fe3O4 nanoparticles. ACS Nano 13:10002–10014

    Article  CAS  Google Scholar 

  10. Alijania H et al (2020) Aptamer-functionalized Fe3O4@MOF nanocarrier for targeted drug delivery and fluorescence imaging of the triple-negative MDA-MB-231 breast cancer cells. J Solid State Chem 292:121680–121690

    Article  Google Scholar 

  11. Ma W-J et al (2019) I-motif-based in situ bipedal hybridization chain reaction for specific activatable imaging and enhanced delivery of antisense oligonucleotides. Anal Chem 91:2538–12545

    Google Scholar 

  12. Bai H-R et al (2020) Conformational conversion enhances cellular uptake of F base double-strand-conjugated oligonucleotides. Anal Chem 92:10375–10380

    Article  CAS  Google Scholar 

  13. Yang Z-Q et al (2019) Investigating adsorption/desorption of DNA on ZIF-8 surface by fluorescently labeled oligonucleotides. Langmuir 35:16290–16296

    Article  CAS  Google Scholar 

  14. Zhang Y et al (2020) Construction of an Iridium(iii)-complex-loaded MOF nanoplatform mediated with a dual-responsive polycationic polymer for photodynamic therapy and cell imaging. Chem Commun 56:762–765

    Article  CAS  Google Scholar 

  15. Chen W et al (2020) Comparison of different zinc precursors for the construction of zeolitic imidazolate framework-8 artificial shells on living cells. Soft Matter 16:270–275

    Article  CAS  Google Scholar 

  16. Feng L-P et al (2018) A high-throughput and sensitive fluorimetric strategy for microRNAs in blood using wettable microwells array and silver nanoclusters with red fluorescence enhanced by metal organic frameworks. ACS Appl Mater Interfaces 10:23647–23656

    Article  CAS  Google Scholar 

  17. Yi J-T et al (2017) Nanoscale zeolitic imidazolate framework-8 for ratiometric fluorescence imaging of microRNA in living cells. Anal Chem 22:12351–12359

    Article  Google Scholar 

  18. Wang Z et al (2021) A bimetallic metal–organic framework encapsulated with DNAzyme for intracellular drug synthesis and self-sufficient gene therapy. Angew Chem Int Ed 60:2–9

    Article  Google Scholar 

  19. Tang Y-F et al (2021) Fluorescent assay of FEN1 activity with nicking enzyme-assisted signal amplification based on ZIF-8 for imaging in living cells. Anal Chem 93:4960–4966

    Article  CAS  Google Scholar 

  20. Guo H et al (2020) One-pot synthesis of darbon dots@zeolitic imidazolate framework-8 composite for enhanced Cu2+ sensing. Anal Methods 12:4058–4063

    Article  CAS  Google Scholar 

  21. Wang K et al (2020) Multifunctional zeolitic imidazolate framework-8 for real-time monitoring ATP fluctuation in mitochondria during photodynamic therapy. Nanoscale 12:15663–15669

    Article  CAS  Google Scholar 

  22. Tang K et al (2021) Multifunctional nano-biosensor based on metal-organic framework for enhanced fluorescence imaging of intracellular miRNA-122 and synergistic chemo-photothermal therapy of tumor cells. Anal Chim Acta 1176:338779–338787

    Article  CAS  Google Scholar 

  23. Gao J-L et al (2021) Light-activated and self-driven autonomous DNA nanomachine enabling fluorescence imaging of microRNA in living cells with exceptional precision and efficiency. ACS Appl Mater Interfaces 13:31485–31494

    Article  CAS  Google Scholar 

  24. Zhao H-X et al (2021) Dual roles of metal-organic frameworks as nanocarriers for miRNA delivery and adjuvants for chemodynamic therapy. ACS Appl Mater Interfaces 13:6034–6042

    Article  CAS  Google Scholar 

  25. Gao P et al (2021) Rational design of a dual-layered metal-organic framework nanostructure for enhancing the cell imaging of molecular beacons. Anal Chem 93:5437–5441

    Article  CAS  Google Scholar 

  26. Zhang J et al (2019) Biomineralized metal-organic framework nanoparticles enable enzymatic rolling circle amplification in living cells for ultrasensitive microRNA imaging. Anal Chem 91:9049–9057

    Article  CAS  Google Scholar 

  27. Pan Y et al (2018) Zeolitic imidazolate framework-based biosensor for detection of HIV-1 DNA. Anal Biochem 546:5–9

    Article  CAS  Google Scholar 

  28. Alsaiari SK et al (2018) Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. J Am Chem Soc 140:143–146

    Article  CAS  Google Scholar 

  29. Zhang J et al (2020) Biomineralized metal-organic framework nanoparticles enable a primer exchange reaction-based DNA machine to work in living cells for imaging and gene therapy. Chem Sci 11:7092–7101

    Article  CAS  Google Scholar 

  30. Ling Y et al (2022) ZIF-8@GMP-Tb nanocomplex for ratiometric fluorescent detection of alkaline phosphatase activity. Spectrochim Acta A Mol Biomol Spectro 264:120230–120236

    Article  CAS  Google Scholar 

  31. Liu N et al (2019) Ratiometric fluorescent detection of Cu2+ based on dual-emission ZIF-8@rhodamine-B nanocomposites. Luminescence 34:193–199

    Article  CAS  Google Scholar 

  32. Hu H et al (2021) Autonomous operation of 3D DNA walkers in living cells for microRNA imaging. Nanoscale 13:1863–1868

    Article  CAS  Google Scholar 

  33. Wang S-M et al (2020) DNA adsorption on nanoscale zeolitic imidazolate framework-8 enabling rational design of a DNA-based nanoprobe for gene detection and regulation in living cells. RSC Adv 10:31012–31021

    Article  CAS  Google Scholar 

  34. Gao J-L et al (2021) Light-activated and self-driven autonomous DNA nanomachine enabling fluorescence imaging of MicroRNA in living cells with exceptional precision and efficiency. ACS Appl Mater Interfaces 13:31485–31494

    Article  CAS  Google Scholar 

Download references

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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Contributions

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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Correspondence to Lingyun Wang or Changqun Cai.

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The authors declare no competing interests.

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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

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