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Hybrid chalcogen bonds in prodrug nanoassemblies provides dual redox-responsivity in the tumor microenvironment

Author

Listed:
  • Tian Liu

    (Shenyang Pharmaceutical University)

  • Lingxiao Li

    (Shenyang Pharmaceutical University)

  • Shuo Wang

    (Shenyang Pharmaceutical University)

  • Fudan Dong

    (Shenyang Pharmaceutical University)

  • Shiyi Zuo

    (Shenyang Pharmaceutical University)

  • Jiaxuan Song

    (Shenyang Pharmaceutical University)

  • Xin Wang

    (Shenyang Pharmaceutical University)

  • Qi Lu

    (Shenyang Pharmaceutical University)

  • Helin Wang

    (Shenyang Pharmaceutical University)

  • Haotian Zhang

    (Shenyang Pharmaceutical University)

  • Maosheng Cheng

    (Shenyang Pharmaceutical University)

  • Xiaohong Liu

    (Shenyang Pharmaceutical University)

  • Zhonggui He

    (Shenyang Pharmaceutical University)

  • Bingjun Sun

    (Shenyang Pharmaceutical University)

  • Jin Sun

    (Shenyang Pharmaceutical University)

Abstract

Sulfur bonds, especially trisulfide bond, have been found to ameliorate the self-assembly stability of homodimeric prodrug nanoassemblies and could trigger the sensitive reduction-responsive release of active drugs. However, the antitumor efficacy of homodimeric prodrug nanoassemblies with single reduction-responsivity may be restricted due to the heterogeneous tumor redox microenvironment. Herein, we replace the middle sulfur atom of trisulfide bond with an oxidizing tellurium atom or selenium atom to construct redox dual-responsive sulfur-tellurium-sulfur and sulfur-selenium-sulfur hybrid chalcogen bonds. The hybrid chalcogen bonds, especially the sulfur-tellurium-sulfur bond, exhibit ultrahigh dual-responsivity to both oxidation and reduction conditions, which could effectively address the heterogeneous tumor microenvironment. Moreover, the hybrid sulfur-tellurium-sulfur bond promotes the self-assembly of homodimeric prodrugs by providing strong intermolecular forces and sufficient steric hindrance. The above advantages of sulfur-tellurium-sulfur bridged homodimeric prodrug nanoassemblies result in the improved antitumor efficacy of docetaxel with satisfactory safety. The exploration of hybrid chalcogen bonds in drug delivery deepened insight into the development of prodrug-based chemotherapy to address tumor redox heterogeneity, thus enriching the design theory of prodrug-based nanomedicines.

Suggested Citation

  • Tian Liu & Lingxiao Li & Shuo Wang & Fudan Dong & Shiyi Zuo & Jiaxuan Song & Xin Wang & Qi Lu & Helin Wang & Haotian Zhang & Maosheng Cheng & Xiaohong Liu & Zhonggui He & Bingjun Sun & Jin Sun, 2022. "Hybrid chalcogen bonds in prodrug nanoassemblies provides dual redox-responsivity in the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35033-7
    DOI: 10.1038/s41467-022-35033-7
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    References listed on IDEAS

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    1. Bingjun Sun & Cong Luo & Xuanbo Zhang & Mengran Guo & Mengchi Sun & Han Yu & Qin Chen & Wenqian Yang & Menglin Wang & Shiyi Zuo & Pengyu Chen & Qiming Kan & Haotian Zhang & Yongjun Wang & Zhonggui He , 2019. "Probing the impact of sulfur/selenium/carbon linkages on prodrug nanoassemblies for cancer therapy," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
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