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Aptamer-coded DNA nanoparticles for targeted doxorubicin delivery using pH-sensitive spacer

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Abstract

An anticancer drug delivery system consisting of DNA nanoparticles synthesized by rolling circle amplification (RCA) was developed for prostate cancer membrane antigen (PSMA) targeted cancer therapy. The template of RCA was a DNA oligodeoxynucleotide coded with PSMA-targeted aptamer, drug-loading domain, primer binding site and pH-sensitive spacer. Anticancer drug doxorubicin, as the model drug, was loaded into the drug-loading domain (multiple GC-pair sequences) of the DNA nanoparticles by intercalation. Due to the integrated pH-sensitive spacers in the nanoparticles, in an acidic environment, the cumulative release of doxorubicin was far more than the cumulative release of the drug in the normal physiological environment. In cell uptake experiments, treated with doxorubicin loaded DNA nanoparticles, PSMA-positive C4-2 cells could take up more doxorubicin than PSMA-null PC-3 cells. The prepared DNA nanoparticles showed the potential as drug delivery system for PSMA targeting prostate cancer therapy.

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Acknowledgements

This work was supported in part by National Key Research and Development Plan (2016YFE0119200) and the National Natural Science Foundation of China (Grant Nos. 81402856, A3 project-81361140344 and 21402143). This research was also partially sponsored by Tianjin Municipal Science and Technology Commission (15JCYBJC28700 and 15JCQNJC13600) and National Students’ Innovation and Entrepreneurship Training Program (201510062008).

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Authors and Affiliations

  1. State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China

    Pengwei Zhang, Junxiao Ye, Ergang Liu, Junbo Gong & Victor C. Yang

  2. Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostic), Tianjin Medical University, Tianjin, 300072, China

    Pengwei Zhang, Ergang Liu, Lu Sun, Jiacheng Zhang, Junbo Gong & Huining He

  3. Department of Pharmacy, Ewha Womans University, Seoul, 120-750, Korea

    Seung-Jin Lee

  4. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Michigan, MI, 48109-1065, USA

    Victor C. Yang

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  1. Pengwei Zhang
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  2. Junxiao Ye
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  3. Ergang Liu
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  4. Lu Sun
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  5. Jiacheng Zhang
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  6. Seung-Jin Lee
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  7. Junbo Gong
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  8. Huining He
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  9. Victor C. Yang
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Corresponding authors

Correspondence to Junbo Gong, Huining He or Victor C. Yang.

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Zhang, P., Ye, J., Liu, E. et al. Aptamer-coded DNA nanoparticles for targeted doxorubicin delivery using pH-sensitive spacer. Front. Chem. Sci. Eng. 11, 529–536 (2017). https://doi.org/10.1007/s11705-017-1645-z

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  • DOI: https://doi.org/10.1007/s11705-017-1645-z

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