Article

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

  • Nature Biomedical Engineering 1745757 (2017)
  • doi:10.1038/s41551-017-0130-9
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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.

Author information

Author notes

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

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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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Youqing Shen.

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