乳腺癌的靶向治疗近年来受到了广泛的关注，然而由于肿瘤复杂的免疫微环境，靶向治疗的方法拓展和联合应用还有待新的突破。我们在前期研究中优化并制备了携带光动力学治疗用光敏剂的纳米颗粒，利用巨噬细胞能被招募并作用于肿瘤免疫微环境的天然特性，有机联合了乳腺癌免疫微环境重构调节和深部靶向光动力学治疗。本研究拟：1）利用细胞代谢修饰工程学设计出表面表达特殊分子（如环状RGD肽段）修饰型的巨噬细胞，利用其内吞作用携载治疗物质（如光敏剂），形成靶向乳腺癌免疫微环境的治疗系统；2）深入研究代谢修饰型巨噬细胞治疗系统对乳腺癌免疫微环境的重构影响和作用机制；3）依据前期我们对乳腺癌免疫微环境中干性及炎性的研究成果，进一步开发多种针对乳腺癌免疫环境调控的修饰型巨噬细胞治疗系统，并验证其治疗效果。本研究不仅为乳腺癌免疫调控的机制研究建立了更加高效的工具，同时改造乳腺癌微环境的免疫治疗提供新的概念和临床转化方法。

Targeted therapy for breast cancer has received widespread attention in recent years. However, due to the complex immune microenvironment of tumor, developing the methods and combining more strategies should be made breakthroughs in the targeted therapy. In the previous study, we optimized the photosensitizer-loaded nanoparticles, and targeted deep tumor tissues using the macrophage biological nature of being recruited in and influencing the tumor immune microenvironment. This system combines breast cancer immune microenvironment remodeling and targeted photodynamic therapy. In this research, we plan to: 1) Design a modified macrophage with the surface-linked molecular (such as cyclic RGD peptide) based on the cellular metabolism modification engineering and complete the targeted transport system by therapeutic substance (such as photosensitizer) loading using macrophage endocytosis; 2) Study the regulatory function of the system by surface modified macrophages based on cellular metabolism in breast cancer immune microenvironment remodeling; 3) Based on the previous research on the stemness and inflammatory properties of breast cancer immune microenvironment, develop more macrophage transport systems which can target the breast cancer immune microenvironment and verify their effect. Our research establishes more optimized tools for the study of breast cancer immune regulation mechanisms, and brings theoretical foundation and new approach to the transformation of breast cancer immunotherapy.