Nanotherapeutics for Macrophage Network Modulation in Tumor Microenvironments: Targets and Tools

Renwei Li,1,* Jing Huang,2,* Yuhao Wei,1 Yusha Wang,1,3 Can Lu,4,5 Jifeng Liu,6,7 Xuelei Ma1 1Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 3Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 4Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 6Department of Otolaryngology Head and Neck Surgery/Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 7State Key Laboratory of Intelligent Construction and Healthy Operation and Maintenance of Deep Underground Engineering, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Can Lu; Jifeng Liu, Email [email protected]; [email protected]: Macrophage is an important component in the tumor immune microenvironment, which exerts significant influence on tumor development and metastasis. Due to their dual nature of promoting and suppressing inflammation, macrophages can serve as both targets for tumor immunotherapy and tools for treating malignancies. However, the abundant infiltration of tumor-associated macrophages dominated by an immunosuppressive phenotype maintains a pro-tumor microenvironment, and engineering macrophages using nanotechnology to manipulate the tumor immune microenvironment represent a feasible approach for cancer immunotherapy. Additionally, considering the phagocytic and specifically tumor-targeting capabilities of M1 macrophages, macrophages manipulated through cellular engineering and nanotechnology, as well as macrophage-derived exosomes and macrophage membranes, can also become effective tools for cancer treatment. In conclusion, nanotherapeutics targeting macrophages remains immense potential for the development of macrophage-mediated tumor treatment methods and will further enhance our understanding, diagnosis, and treatment of various malignants.Keywords: engineered macrophages, nanomedicine, cancer therapy, anti-tumor immunity