肿瘤相关巨噬细胞（TAM）与肿瘤的发生、发展和转移密切相关。靶向TAM的治疗成为肿瘤治疗的研究热点之一，因此如何实现高效精准靶向TAM是个亟待解决的问题。本课题根据肿瘤血管和肿瘤相关巨噬细胞表面的特殊性质，设计一个先靶向肿瘤血管，并能高效跨过肿瘤血管屏障进而靶向TAM的逐级式多功能纳米给药系统。该系统采用聚乙二醇/聚乳酸-羟基乙酸（PEG/PLGA）组成的两亲性嵌段共聚物作为纳米递送体系，以针对血小板衍生生长因子受体-β（PDGFR-β）和集落刺激因子-1受体（CSF-1R）的抗体为双重靶向定位的载体材料，同时装载PI3Kγ抑制剂来抑制TAM，提高肿瘤的治疗疗效；采取基于生物正交化学的预靶向策略标记放射性核素Ga-68，用于PET/CT显像，并建立一种定量的可视化方法实时评价TAM数量及活性，为探索以肿瘤微环境中TAM为靶点的新型肿瘤治疗途径提供理论基础和实验依据。

Tumor Associated macrophages (TAMs) are closely related to the occurrence, development and metastasis of tumors. TAM targeted therapy has become an important development direction of cancer research, so that efficient and accurate targeting of TAM is an urgent problem to be solved. In this research, we design a multifunctional nano drug delivery system according to the specific properties of tumor blood vessels and the surface of TAM. The nanoparticles will stepwise and continually bind with tumor blood vessels, cross the barrier tumor blood vessels efficiently and then target TAMs. Polyethylene glycol /poly lactic acid - glycolic acid (PEG/PLGA) of the amphiphilic block copolymer will be used as nano delivery system, and antibodies against platelet-derived growth factor receptor-β (PDGFR-β) and colony stimulating factor 1 receptor (CSF-1R) will be used as the dual targeting carrier. PI3K gamma inhibitors will be loaded to suppress TAMs, and improve the treatment efficacy of tumor. Radionuclide gallium-68 (Ga-68) was labeled to the nanoparticles for PET/CT imaging according to pretargeting strategy based on biological orthogonal chemical tag. The quantity and the activity of TAM will be evaluated visually and in real-time. This research explores a new system for TAM targeting imaging and treatment.