Preclinical Nanoparticle Approaches Targeting Tumor-Associated Macrophages in Breast Cancer: From Mechanisms to Therapeutic Strategies

Jiahui Teng,1,2 Xiaorong Zhang,2 Chunxiao Shen,1,2 Ling Wang,2 Jiali Hu,2 Zefen Li,1,2 Yan Liu,2,3 Jinyan Liu,1,2 Shufei Wei,1,2 Liangliang Wang1,2 1The First Clinical Medical School, Jiujiang University, Jiujiang, Jiangxi,People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, People’s Republic of China; 3The First Clinical Medical School, Gannan Medical University, Ganzhou, Jiangxi, People’s Republic of ChinaCorrespondence: Shufei Wei; Liangliang Wang, Email weishufei0429@163.com; jjwangliangliang@163.comAbstract: Breast cancer is the most common malignancy among women worldwide, with high incidence and mortality rates. Tumor-associated macrophages (TAMs) are key mediators in the immunosuppressive tumor microenvironment (TME), contributing to poor prognosis and reducing immunotherapy efficacy. This review examines the dual roles of TAMs in breast cancer progression. TAMs are known to promote tumor development through angiogenesis, immune evasion, and metastasis, while M1-polarized TAMs conversely enhance antitumor immunity. Herein, the nanoparticle-based strategies targeting TAMs presented in preclinical research are explored, including reprogramming M2 to M1 macrophages, delivering MYC inhibitors, depleting TAMs, and inhibiting TAM recruitment. Integration with immune checkpoint inhibitors is also discussed. Challenges in translating these nanoparticle approaches from preclinical models to clinical practice are further addressed, with an emphasis placed on human-relevant models, optimized production processes, and personalized therapeutic approaches.Keywords: breast cancer, tumor-associated macrophages, nanotechnology, nanoparticles, M1/M2 Polarization, immune checkpoint inhibitors