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A non-cytotoxic dendrimer with innate and potent anticancer and anti-metastatic activities

Nature Biomedical Engineering volume 1, pages 745–757 (2017)Cite this article

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Abstract

The structural perfection and multivalency of dendrimers have made them useful for biodelivery and bioactivity via peripheral functionalization and the modulation of core-forming structures and dendrimer generations. Yet only few dendrimers have shown inherent therapeutic activity arising from their inner repeating units. Here, we report the synthesis and characterization of a polyacylthiourea dendrimer with inherent potent anticancer activity and the absence of cytotoxicity in mice. The poly(ethylene glycol)-functionalized fourth generation of the dendrimer, which can be efficiently synthesized from sequential click reactions of orthogonal monomers, displays low in vivo acute and subacute toxicities yet potently inhibits tumour growth and metastasis. The dendrimer’s in vivo anticancer activity arises from the depletion of bioavailable copper and the subsequent inhibition of angiogenesis and cellular proliferation. When compared with some clinically used cytotoxin drugs, the dendrimer exerts inherent anticancer activity via non-cytotoxic pathways and leads to higher therapeutic efficacy, yet without cytotoxin-induced side effects.

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Acknowledgements

We thank the National Basic Research Program of China (2014CB931900), the National Natural Science Foundation of China (51390481, U1501243, 51522304, 21090352 and 50888001) and the Doctoral Fund of Ministry of Education of China (20110101130007) for financial support.

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  1. Shiqun Shao and Quan Zhou contributed equally to this work.

Authors and Affiliations

  1. Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, China

    Shiqun Shao, Quan Zhou, Jingxing Si, Jianbin Tang, Xiangrui Liu & Youqing Shen

  2. The Second Affiliated Hospital of School of Medicine, Zhejiang University, 310009, Hangzhou, China

    Jingxing Si, Kai Wang & Rongzhen Xu

  3. College of Pharmaceutical Science, Zhejiang University, 310058, Hangzhou, China

    Meng Wang & Jianqing Gao

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  1. Shiqun Shao
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Contributions

Y.S. designed and supervised the project and wrote the manuscript with S.S.; S.S. Q.Z. and J.S. carried out all the experiments; M.W. checked the anticancer activity; X.L., J.G., R.X. and K.W. instructed the bioassays; J.T. instructed the synthesis.

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Shao, S., Zhou, Q., Si, J. et al. A non-cytotoxic dendrimer with innate and potent anticancer and anti-metastatic activities. Nat Biomed Eng 1, 745–757 (2017). https://doi.org/10.1038/s41551-017-0130-9

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