Bone-marrow endothelial cells in the haematopoietic stem-cell niche form a network of blood vessels that regulates blood-cell traffic as well as the maintenance and function of haematopoietic stem and progenitor cells. Here, we report the design and in vivo performance of systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA (siRNA), for the silencing of genes in bone-marrow endothelial cells. In mice, nanoparticles encapsulating siRNA sequences targeting the proteins stromal-derived factor 1 (Sdf1) or monocyte chemotactic protein 1 (Mcp1) enhanced (when silencing Sdf1) or inhibited (when silencing Mcp1) the release of stem and progenitor cells and of leukocytes from the bone marrow. In a mouse model of myocardial infarction, nanoparticle-mediated inhibition of cell release from the haematopoietic niche via Mcp1 silencing reduced leukocytes in the diseased heart, improved healing after infarction and attenuated heart failure. Nanoparticle-mediated RNA interference in the haematopoietic niche could be used to investigate haematopoietic processes for therapeutic applications in cancer, infection and cardiovascular disease.

造血干细胞生态位中的骨髓内皮细胞形成血管网络，调节血细胞运输以及造血干细胞和祖细胞的维持和功能。在这里，我们报告了系统注射脂质聚合物纳米颗粒的设计和体内性能，该纳米颗粒封装了小干扰RNA（siRNA），用于沉默骨髓内皮细胞中的基因。在小鼠中，封装针对基质衍生因子 1 (Sdf1) 或单核细胞趋化蛋白 1 (Mcp1) 蛋白的 siRNA 序列的纳米粒子增强（当沉默Sdf1时）或抑制（当沉默Mcp1时）干细胞和祖细胞以及白细胞的释放骨髓。在心肌梗塞小鼠模型中，纳米颗粒介导的通过沉默Mcp 1来抑制造血生态位中的细胞释放，减少了患病心脏中的白细胞，改善了梗塞后的愈合并减轻了心力衰竭。造血生态位中纳米颗粒介导的 RNA 干扰可用于研究造血过程，用于癌症、感染和心血管疾病的治疗应用。