甘露糖受体介导复合纳米微粒用于肿瘤相关巨噬细胞显像与治疗的研究

肿瘤相关巨噬细胞（TAM）在肿瘤发生、发展及转归中起重要作用，TAM已成为肿瘤治疗的一个新的重要靶点。靶向TAM的显像对肿瘤治疗与预后评估具有重要作用。本研究采用纳米技术，以纳米脂质体为载体，同时装载铜-64（Cu-64）、诱导TAMs凋亡的氯膦酸盐、TAM表面甘露糖受体的配体，通过酸敏感的键连接的PEG包裹，避免纳米脂质体被肝脾的巨噬细胞吞噬，同时又保证PEG在肿瘤微环境中断裂而暴露甘露糖，使其与TAM表面受体结合，介导TAM吞噬纳米脂质体复合物。对纳米脂质体复合物的特性进行鉴定，并对其在体内外与TAM结合的特异性、血液动力学、体内分布、体内毒性进行研究。采用PET/CT显像，比较肿瘤模型与炎症模型纳米复合体分布差异；确定最佳显像时间，并研究TAM数量与肿瘤部位放射性分布的关系，建立一种实时评价TAM数量及活性的定量、可视化方法。通过观察药物的疗效与毒性，评价纳米复合物的载药性能。

? Tumor associated macrophage (TAM) plays important roles in cancer growth and metastasis. TAM targeted therapy has been a promising new avenue in cancer treatment in recent years. As a result, TAM specific imaging has drawn great interests for its application in evaluation of treatment response and prognosis. We propose a M2 macrophage targeting nanoparticle probe for M2 TAM imaging and inhibition. It is a Pegylated liposome that encapsulates Cu-64 and cyanin 7 for PET and microscopic imagings, clodronates as therapeutic agent. The acid sensitive PEG moiety on surface is designed to inhibit kupffer cell clearance and enhance TAM uptake. The surface mannose moiety will guide the liposome targeting to M2 TAM. The complex will be constructed and evaluated for its properties. Biological properties such as cell uptake,blood clearance, stability, distribution, toxicity etc will be determined. The targeting property will also be evaluated in vivo by PET/CT.The efficacy of the targeted therapy of clodranates delivered by the liposome will be evaluated determined at end of the project.