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Engineering a customized nanodrug delivery system at the cellular level for targeted cancer therapy

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Abstract

Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411, and a replaceable anti-biomarker probe (ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21505039, 2013CB932702), the China National Instrumentation Program (2011YQ03012412) and the National Institutes of Health grants (GM079359, CA133086).

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Authors and Affiliations

  1. Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences, Aptamer Engineering Center of Hunan Province, Hunan University, Hunan, 410082, China

    Jin Li, Liping Qiu, Sitao Xie, Jing Zhang, Liqin Zhang, Honglin Liu, Xiaobing Zhang & Weihong Tan

  2. Center for Research at Bio/Nano Interface, Department of Chemistry and Department of Physiology and Functional Genomics, Health Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida, 32611-7200, USA

    Liqin Zhang & Weihong Tan

  3. Key Laboratory for Analytical Science of Food Safety and Biology (Ministry of Education), College of Chemistry, Fuzhou University, Fuzhou, 350116, China

    Juan Li

Authors
  1. Jin Li
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  2. Liping Qiu
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  3. Sitao Xie
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  4. Jing Zhang
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  5. Liqin Zhang
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  6. Honglin Liu
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  7. Juan Li
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  8. Xiaobing Zhang
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  9. Weihong Tan
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Corresponding authors

Correspondence to Liping Qiu or Weihong Tan.

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Li, J., Qiu, L., Xie, S. et al. Engineering a customized nanodrug delivery system at the cellular level for targeted cancer therapy. Sci. China Chem. 61, 497–504 (2018). https://doi.org/10.1007/s11426-017-9176-3

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  • DOI: https://doi.org/10.1007/s11426-017-9176-3

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