2. Academic Validation
  3. Hematopoietic stem and progenitor cell membrane-coated vesicles for bone marrow-targeted leukaemia drug delivery

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

  • Nat Commun. 2024 Jul 7;15(1):5689. doi: 10.1038/s41467-024-50021-9.
Jinxin Li # 1 2 3,  Honghui Wu # 4 5 6,  Zebin Yu # 1 2 3,  Qiwei Wang # 1 2 3,  Xin Zeng # 1 2 3,  Wenchang Qian 1 2 3,  Siqi Lu 1 2 3,  Lingli Jiang 1 2 3,  Jingyi Li 1 2 3,  Meng Zhu 1 2 3,  Yingli Han 1 2 3,  Jianqing Gao 7 8 9 10 11,  Pengxu Qian 12 13 14
Affiliations

Affiliations

  • 1 Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 2 Liangzhu Laboratory, Zhejiang University, 1369 West Wenyi Road, Hangzhou, 311121, China.
  • 3 Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, 310058, China.
  • 4 State Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 5 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
  • 6 Jinhua Institute of Zhejiang University, Jinhua, 321002, Zhejiang, PR China.
  • 7 State Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. gaojianqing@zju.edu.cn.
  • 8 Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China. gaojianqing@zju.edu.cn.
  • 9 Jinhua Institute of Zhejiang University, Jinhua, 321002, Zhejiang, PR China. gaojianqing@zju.edu.cn.
  • 10 Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, PR China. gaojianqing@zju.edu.cn.
  • 11 Zhejiang University Cancer Center, Zhejiang University, Hangzhou, 310058, PR China. gaojianqing@zju.edu.cn.
  • 12 Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. axu@zju.edu.cn.
  • 13 Liangzhu Laboratory, Zhejiang University, 1369 West Wenyi Road, Hangzhou, 311121, China. axu@zju.edu.cn.
  • 14 Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, 310058, China. axu@zju.edu.cn.
  • # Contributed equally.
PMID: 38971796 DOI: 10.1038/s41467-024-50021-9
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.

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