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Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles

Author

Listed:
  • Jing Qi

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Feiyang Jin

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Yuchan You

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Yan Du

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Di Liu

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Xiaoling Xu

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Jun Wang

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Luwen Zhu

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Minjiang Chen

    (College of Pharmaceutical Sciences, Zhejiang University)

  • Gaofeng Shu

    (Lishui Hospital of Zhejiang University)

  • Liming Wu

    (The First Affiliated Hospital, Zhejiang University School of Medicine)

  • Jiansong Ji

    (Lishui Hospital of Zhejiang University)

  • Yongzhong Du

    (College of Pharmaceutical Sciences, Zhejiang University)

Abstract

Some specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge.

Suggested Citation

  • Jing Qi & Feiyang Jin & Yuchan You & Yan Du & Di Liu & Xiaoling Xu & Jun Wang & Luwen Zhu & Minjiang Chen & Gaofeng Shu & Liming Wu & Jiansong Ji & Yongzhong Du, 2021. "Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24902-2
    DOI: 10.1038/s41467-021-24902-2
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    Cited by:

    1. Zhiqi Zhang & Xiaoxuan Xu & Jiawei Du & Xin Chen & Yonger Xue & Jianqiong Zhang & Xue Yang & Xiaoyuan Chen & Jinbing Xie & Shenghong Ju, 2024. "Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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