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A microRNA-21-responsive doxorubicin-releasing sticky-flare for synergistic anticancer with silencing of microRNA and chemotherapy

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Abstract

A sticky-flare gold nanoparticle probe (AuNP-probe) is designed by the combination of locked nucleic acid functionalized silencing of microRNA technology for intracellular microRNA-21 (miRNA-21) sensitively detecting, fluorescence imaging, localizing and silencing. The limit of detection is as low as 0.01 nM. Overexpressed miRNA-21 in cancer cells serves as endogenous drug release stimuli to trigger the release of probe-loaded doxorubicin (Dox), which soon translocates into cell nuclei. This multifunctional Dox-loaded AuNP-probe (Dox-AuNP-probe) could induce cancer cell apoptosis effectively through the synergistic effect of gene silencing and chemotherapy. This Dox-AuNP-probe exhibits superior drug potency compared to free Dox molecules, with a cell inhibition rate of 57% (but only 20% for Dox) to wild-type cancer cells and 30% (but 0% for Dox) to drug-resistent cancer cells after 72 h, and this strategy not only has the function of sensing, but also can effectively bypass drug resistance. In MCF-7 xenograft tumor-bearing mice, the Dox-AuNP-probes show greater inhibition for tumor tissues than miRNA-21 targeted AuNP-probes (Targeting-AuNP-probe) or free Dox molecules. Therefore, the Dox-AuNP-probe represents a promising nanotheranostic platform for future applications in cancer molecular imaging and therapy, especially providing a potential strategy to treat resistant cancers.

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Acknowledgements

This work was supported by the Natural Science Foundation of Shandong Province (ZR2015BM024), “Shandong Province Tai-Shan Program”, China Scholarship Council (CSC) scholarship to Dr. Hong, and the National Natural Science Foundation of China (21729501).

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, 252059, China

    Min Hong, Hongxiao Sun, Qiangqiang Yang, Shuxian Yu, Shuhua Fan & Chuan Li

  2. School of Agriculture, Liaocheng University, Liaocheng, 252059, China

    Shuang Cheng

  3. Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, 410082, China

    Cheng Cui & Weihong Tan

  4. Department of Pharmacy, Tai’an Municipal Hospital, Tai’an, 271000, China

    Hongxiao Sun

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  1. Min Hong
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  2. Hongxiao Sun
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  3. Qiangqiang Yang
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  4. Shuang Cheng
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  7. Chuan Li
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  8. Cheng Cui
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  9. Weihong Tan
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Correspondence to Min Hong or Weihong Tan.

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A microRNA-21-responsive doxorubicin-releasing sticky-flare for synergistic anticancer with silencing of microRNA and chemotherapy

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Hong, M., Sun, H., Yang, Q. et al. A microRNA-21-responsive doxorubicin-releasing sticky-flare for synergistic anticancer with silencing of microRNA and chemotherapy. Sci. China Chem. 64, 1009–1019 (2021). https://doi.org/10.1007/s11426-020-9973-9

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  • DOI: https://doi.org/10.1007/s11426-020-9973-9

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