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Investigation of the Sequential Actions of Doxorubicin and p53 on Tumor Cell Growth Via Branched Polyethylenimine-β-cyclodextrin Conjugates

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Abstract

The combination of gene therapy and chemotherapy has showed increased therapeutic efficacy in the treatment of cancers, but it is not well investigated about the actual coordination pattern between therapeutic gene and chemical drug. In this work, p53/BPEI-β-CD/AD-dox complex was fabricated and employed to investigate the interaction manner between p53 and doxorubicin (Dox). Briefly, branched polyethylenimine (BPEI) was conjugated with β-cyclodextrin hydrate (β-CD) to form BPEI-β-CD backbone, and p53 plasmid was condensed by positively charged BPEI via electrostatic interaction, while Dox was first conjugated with adamantine (AD) and then assembled with BPEI-β-CD backbone via the host–guest interaction. It was found that the BPEI-β-CD backbone possessed high endocytosis efficiency but low cytotoxicity. Moreover, p53/BPEI-β-CD/AD-dox complex released Dox and enabled the expression of p53 gene in a sequential manner, and the released Dox and expressed p53 gene showed successive inhibition of the growth of HeLa cells in vitro. With the ability to co-deliver chemical drug and therapeutic gene and exert their inhibitory actions on tumor cell growth in a sequential manner, this DNA/BPEI-β-CD/AD-drug complex via electrostatic interaction and host–guest assembly not only achieved long-term efficacy in inhibiting tumor cell growth but also can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for other purposes.

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Acknowledgments

This work was funded by National Natural Science Foundation of China (31200727, H. Nie; 31300788, X. Zhang), Natural Science Foundation of Hunan Province (2015JJ1007, H. Nie), and Hunan University Fund for Interdisciplinary Research (2015JCA02, H. Nie). The authors wish to confirm that there are no known conflicts of interest associated with this publication.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Hunan University, Yuelu Mountain, Yuelu District, Changsha, 410082, Hunan, China

    Bei Xie, Jian Peng, Shuo Wang & Hemin Nie

  2. Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, No. 72, Wenhua Road, Shenhe District, Shenyang, 110016, Liaoning, China

    Xing Zhang

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  1. Bei Xie
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Correspondence to Hemin Nie.

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Associate Editor James J. Moon oversaw the review of this article.

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Xie, B., Peng, J., Wang, S. et al. Investigation of the Sequential Actions of Doxorubicin and p53 on Tumor Cell Growth Via Branched Polyethylenimine-β-cyclodextrin Conjugates. Ann Biomed Eng 44, 3372–3383 (2016). https://doi.org/10.1007/s10439-016-1627-1

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