慢性粒细胞白血病（CML）是一种造血干细胞恶性克隆性疾病，病位在骨髓。骨髓干细胞龛中白血病干细胞的存在导致BCR-ABL抑制剂虽能有效缓解CML慢性期患者症状但不能治愈CML，如何有效清除干细胞龛中的白血病干细胞成为治愈CML的关键科学问题。砒霜主要成分三氧化二砷能通过降解BCR-ABL蛋白、促进白血病干细胞分化和克服干细胞龛庇护等多种药理机制清除白血病干细胞。本项目基于中医治病求本原则构建一种新型靶向骨髓干细胞龛的双重多肽修饰纳米给药系统。采用反胶束原理将三氧化二砷以砷镍过渡态结晶形式包载于聚合物纳米粒中，提高载药效率和稳定性；借助双重多肽介导将载药纳米粒递送到两类干细胞龛：骨内膜龛和血管龛；龛内纳米粒被细胞摄取后砷镍结晶在内涵体酸性环境释放三价砷，通过其综合药理机制有效清除白血病干细胞，解决当前CML治疗关键难题，为利用干细胞龛靶向策略治疗其它骨髓恶性肿瘤提供新思路。

Chronic myeloid leukemia (CML) is one type of clonogenic hematopoietic stem cell diseases originated from bone marrow. Although BCR-ABL tyrosine kinase inhibitors are remarkably effective in inducing remission in chronic phase patients, they are not curative in a majority of patients due to their failure to eradicate leukemia stem cells (LSCs) inside bone marrow stem cell niches. Therefore, how to deliver therapeutic agent into stem cell niches to eradicate LSCs is the key to cure CML. Arsenic trioxide can remove LSCs via its multiple pharmacological activities such as autophagic degradation of BCR-ABL protein, priming LSCs differentiation and destroying the sanctuary of stem cell niches etc. Here, we construct a novel dual-peptide modified nanocarrier to target bone marrow stem niches according to the Chinese medicine theory of treatment aiming at its pathogenesis. We encapsulate As-Ni transitional metal compound into dual-peptide conjugated nanoparticles based on reverse micelles rationale. The loading density and stability of arsenic trioxide in nanoparticles are improved. The dual-peptide conjugated nanoparticles have the ability to deliver arsenic trioxide into stem cell niches including endosteal niches and vascular niches. Trivalent arsenic can be released via As-Ni compound dissociation among acidic conditions of endosomes after cellular uptake of nanoparticles inside niches. The CML-LSCs are finally eradicated by trivalent arsenic via its combined molecular activities. This stem cell niches targeted delivery strategy has the potential to be used in other malignant hematologic disorders treatment.