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Amphiphilic drug-drug conjugate for cancer therapy with combination of chemotherapeutic and antiangiogenesis drugs

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Abstract

The progression and metastasis of solid tumors strongly rely on the process of forming nascent blood vessels. However, using angiogenesis inhibitors alone does not meet the cancer treatment needs. Herein, we used the amphiphilic drug-drug conjugate (ADDC) strategy to fabricate a new drug conjugate with the combination of chemotherapeutic drug and antiangiogenesis drug together. With one-step esterification of hydrophilic floxuridine (FUDR) and hydrophobic pseudolaric acid B (PAB), the conjugate was synthesized. The amphiphilic property of FUDR-PAB conjugate induced the self-assembly to form nanoparticles in water. From further in vitro and in vivo experiments, this FUDR-PAB conjugate does not only have a high antitumor effect, but also shows efficient antianiogenesis property. These results offer a promising ADDC strategy for designing drugs with combination of chemotherapeutic drug and antiangiogenesis drug together.

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Acknowledgements

This work was supported by the National Basic Research Program (2015CB931801), and the National Natural Science Foundation of China (51690151, 21504055).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, China

    Mo Sun, Qiuhui Qian, Leilei Shi, Li Xu, Linzhu Zhou, Xinyuan Zhu & Deyue Yan

  2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Qunfang Liu & Jian-Min Yue

Authors
  1. Mo Sun
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  2. Qiuhui Qian
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  3. Leilei Shi
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  4. Li Xu
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  5. Qunfang Liu
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  6. Linzhu Zhou
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  7. Xinyuan Zhu
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  8. Jian-Min Yue
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  9. Deyue Yan
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Correspondence to Xinyuan Zhu, Jian-Min Yue or Deyue Yan.

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Conflict of interest The authors declare that they have no conflict of interest.

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Sun, M., Qian, Q., Shi, L. et al. Amphiphilic drug-drug conjugate for cancer therapy with combination of chemotherapeutic and antiangiogenesis drugs. Sci. China Chem. 63, 35–41 (2020). https://doi.org/10.1007/s11426-019-9602-4

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  • DOI: https://doi.org/10.1007/s11426-019-9602-4

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