Zhang Yanqin, Deng Yanfang, Zhai Yuewen, Li Yu, Li Yuting, Li Juequan, Gu Yueqing, Li Siwen
State Key Laboratory of Natural Medicines, Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, China.
Nat Nanotechnol. 2024 Oct;19(10):1558-1568. doi: 10.1038/s41565-024-01736-9. Epub 2024 Jul 23.
Haematologic malignancies commonly arise from the bone marrow lesion, yet there are currently no effective targeted therapies against tumour cells in this location. Here we constructed a bone-marrow-targeting nanosystem, CSF@E-Hn, which is based on haematopoietic-stem-cell-derived nanovesicles adorned with gripper ligands (aPD-L1 and aNKG2D) and encapsulated with colony-stimulating factor (CSF) for the treatment of haematologic malignancies. CSF@E-Hn targets the bone marrow and, thanks to the gripper ligands, pulls together tumour cells and natural killer cells, activating the latter for specific tumour cell targeting and elimination. The therapeutic efficacy was validated in mice bearing acute myeloid leukaemia and multiple myeloma. The comprehensive assessment of the post-treatment bone marrow microenvironment revealed that the integration of CSF into a bone-marrow-targeted nanosystem promoted haematopoietic stem cell differentiation, boosted memory T cell generation and maintained bone homoeostasis, with long-term prevention of relapse. Our nanosystem represents a promising strategy for the treatment of haematologic malignancies.
血液系统恶性肿瘤通常起源于骨髓病变，但目前尚无针对该部位肿瘤细胞的有效靶向治疗方法。在此，我们构建了一种骨髓靶向纳米系统CSF@E-Hn，它基于造血干细胞衍生的纳米囊泡，装饰有抓取配体（抗程序性死亡配体1和抗自然杀伤细胞2D），并包裹有集落刺激因子（CSF），用于治疗血液系统恶性肿瘤。CSF@E-Hn靶向骨髓，并且由于抓取配体，将肿瘤细胞和自然杀伤细胞聚集在一起，激活自然杀伤细胞以特异性靶向和消除肿瘤细胞。在患有急性髓系白血病和多发性骨髓瘤的小鼠中验证了其治疗效果。对治疗后骨髓微环境的综合评估表明，将CSF整合到骨髓靶向纳米系统中可促进造血干细胞分化，增强记忆性T细胞生成并维持骨稳态，长期预防复发。我们的纳米系统代表了一种治疗血液系统恶性肿瘤的有前景的策略。
