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

• Published in: Nature communications Vol. 15; no. 1; pp. 5689 - 17
• Main Authors: Li, Jinxin, Wu, Honghui, Yu, Zebin, Wang, Qiwei, Zeng, Xin, Qian, Wenchang, Lu, Siqi, Jiang, Lingli, Li, Jingyi, Zhu, Meng, Han, Yingli, Gao, Jianqing, Qian, Pengxu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.07.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/100; 631/61/54/989; 631/67/1059; 631/67/1990; Animals; Apoptosis; Apoptosis - drug effects; Biomimetics; Bone marrow; Bone Marrow - drug effects; Bone Marrow - metabolism; Bone Marrow - pathology; CD18 Antigens - metabolism; CD44 antigen; Cell adhesion; Cell adhesion molecules; Cell differentiation; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell membranes; Cell proliferation; Cell Proliferation - drug effects; Chemotherapy; Coated vesicles; Cytarabine; Cytarabine - pharmacology; Drug delivery; Drug Delivery Systems; Effectiveness; Hematopoietic stem cells; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Hemopoiesis; Humanities and Social Sciences; Humans; Hyaluronan Receptors - metabolism; Hyaluronic acid; Hyaluronic Acid - chemistry; Intercellular adhesion molecule 1; Leukemia; Leukemia - drug therapy; Leukemia - pathology; Liposomes; Malignancy; Membrane vesicles; Mice; multidisciplinary; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Osteoprogenitor cells; Progenitor cells; Science; Science (multidisciplinary); Stem cells; Vesicles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50021-9

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. Effective delivery of drugs to bone marrow has potential for leukemia treatment. Here the authors report the delivery of chemotherapy drug Ara-C with HSPC cell membrane derived-biomimetic vesicles, which target leukemia stem cells thereby effectively inhibit its progression.