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Hematopoietic stem and progenitor cell membrane-coated vesicles for bone marrow-targeted leukaemia drug delivery

Author

Listed:
  • Jinxin Li

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Honghui Wu

    (Zhejiang University
    Zhejiang University
    Jinhua Institute of Zhejiang University)

  • Zebin Yu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Qiwei Wang

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Xin Zeng

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Wenchang Qian

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Siqi Lu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Lingli Jiang

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Jingyi Li

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Meng Zhu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Yingli Han

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Jianqing Gao

    (Zhejiang University
    Zhejiang University
    Jinhua Institute of Zhejiang University
    Zhejiang University School of Medicine)

  • Pengxu Qian

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

Abstract

Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin β2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.

Suggested Citation

  • Jinxin Li & Honghui Wu & Zebin Yu & Qiwei Wang & Xin Zeng & Wenchang Qian & Siqi Lu & Lingli Jiang & Jingyi Li & Meng Zhu & Yingli Han & Jianqing Gao & Pengxu Qian, 2024. "Hematopoietic stem and progenitor cell membrane-coated vesicles for bone marrow-targeted leukaemia drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50021-9
    DOI: 10.1038/s41467-024-50021-9
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