Hematopoietic stem cell membrane-coated vesicles for targeted drug delivery to the bone marrow and elimination of leukemia cells

Leukemia is a kind of hematological malignancy originating from bone marrow, whose morbidity and mortality are increasing year by year. The uncertain pathogenesis and lack of effective treatment result in a very low 5-year survival rate in patients. Bone marrow is the key site to provide essential niche signals for the initiation, progression, and recurrence of leukemia. However, in clinical treatment, there is a lack of therapeutic approaches to specifically deliver drugs to the bone marrow. In this study, we developed a biomimetic vesicle, derived from hematopoietic stem and progenitor cells (HSPCs) for the targeted drug delivery to bone marrow and elimination of leukemia. Particularly, we fused HSPC cell membrane and liposomes to prepare biomimetic vesicles, which markedly accumulated in the bone marrow of leukemia mice by interaction with hyaluronic acid through CD44 on the biomimetic vesicles. Moreover, the biomimetic vesicles exhibited specific affinity to the leukemia cells through the ICAM-1/ITGB2 interaction. Further in vivo and in vitro experiments confirmed that the biomimetic vesicles carrying chemotherapy drug Ara-C significantly inhibited the proliferation, induced apoptosis and differentiation, and eliminated the leukemia stem cells. Mechanically, bulk-cell RNA-seq revealed that Ara-C@HSPC-Lipo treatment induced apoptosis and differentiation and reduced cell cycle and oncogenic pathways. Finally, we verified the superior biosafety of the biomimetic vesicles. Overall, this study provides a new method for targeting bone marrow and treating leukemia, and sheds lights into targeting other diseases of bone marrow origin.