鉴于现有基于“EPR效应”设计的肿瘤靶向策略不适于早期肿瘤治疗的客观事实，以及M2型肿瘤相关巨噬细胞（TAM）在肿瘤发生、发展中的重要地位。我们利用TAM来源于单核细胞并具有表型可塑的特点，设计了针对M2型TAM的早期肿瘤治疗方案。即构建唾液酸（SA）修饰唑来膦酸（ZOL）脂质体，借助SA对单核细胞和巨噬细胞的双重亲和特性，提高制剂被单核细胞的摄取效率以及随单核细胞迁移至肿瘤组织后的TAM靶向效率，递送至靶部位的ZOL通过重塑/清除TAM，解除对机体免疫细胞的抑制作用，达到早期肿瘤治疗目的。通过药效实验对该策略进行总体评价；采用活体成像、共聚焦显微镜、免疫组化、ELISA等方法，从组织、细胞和分子水平对M2型TAM的重塑/清除进行考察。本研究利用单核细胞递送SA修饰ZOL脂质体，系统探讨重塑/清除M2型TAM治疗早期肿瘤的可行性，为肿瘤早期药物递送系统的设计提供一个新思路。

In view of the objective fact that the tumour targeting strategy based on "EPR effect" is not suitable for the early tumour therapy, and the important status of the M2-polarised tumour-associated macrophages（TAM）in the whole tumour development. We designed a strategy for early tumour therapy using the characteristics of M2-TAM derived from monocytes and phenotypic plasticity. SA, with double affinity of monocytes and macrophages, was modified on the surface of liposomes loaded with ZOL, so that the liposomes had the ability of both high uptaken efficiency by monocytes and high targeting efficiency to TAM. ZOL would achieve the therapeutic purpose by phenotype remodeling/depletion of TAM when delivered to the targeting site. In this study, the whole evaluation of the early tumour therapy was assessed by in vivo antitumour activity and toxicity. The phenotype remodeling/depletion of M2-TAM was evaluated at the tissue, cell and molecular levels by performing in vivo imaging analysis, confocal microscopy, immunohistochemistry and ELISA. The project systematically explores the feasibility by phenotye remodeling/depletion of M2-TAM based on delivery nanoparticles by monocytes and provides a new way for the for early tumour therapy.