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

Jinxin Li, Honghui Wu, Zebin Yu, Qiwei Wang, Xin Zeng, Wenchang Qian, Siqi Lu, Lingli Jiang, Jingyi Li, Meng Zhu, Yingli Han, Jianqing Gao () and Pengxu Qian ()
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Jinxin Li: Zhejiang University School of Medicine
Honghui Wu: Zhejiang University
Zebin Yu: Zhejiang University School of Medicine
Qiwei Wang: Zhejiang University School of Medicine
Xin Zeng: Zhejiang University School of Medicine
Wenchang Qian: Zhejiang University School of Medicine
Siqi Lu: Zhejiang University School of Medicine
Lingli Jiang: Zhejiang University School of Medicine
Jingyi Li: Zhejiang University School of Medicine
Meng Zhu: Zhejiang University School of Medicine
Yingli Han: Zhejiang University School of Medicine
Jianqing Gao: Zhejiang University
Pengxu Qian: Zhejiang University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50021-9

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