Macrophages play a key role in immune-related diseases and are critical therapeutic targets for immunotherapy. Designing and developing effective therapies for macrophage reprogramming remains challenging. Here, we rationally designed polysaccharide nanoadjuvants to reprogram macrophage functions and enhance immunotherapy for various diseases, aided by high-throughput phenotypic screening using macrophage phenotype-specific nanoprobes (MPSNPr).The MPSNPr exhibits high specificity for the macrophage M1 phenotype, as it forms H aggregates on the exterior surface and the polysaccharide nanocarrier binds to the glucose transporter 1 receptor. Based on this MPSNPr, a high-throughput platform was constructed and used to screen various drugs for macrophage reprogramming, capable of identifying pro-inflammatory and anti-inflammatory candidate drugs. The polysaccharide nano-adjuvants Dex-BA and Dex-SAL were rationally engineered with two effective candidate drugs to enhance the efficacy of macrophage reprogramming both in vitro and in vivo.In a mouse melanoma model, Dex-BA significantly inhibited tumor growth by inducing macrophage M1 polarization, dendritic cell maturation, and cytotoxic T cell activation. Dex-SAL alleviated symptoms of rheumatoid arthritis and reduced inflammation by reprogramming activated macrophages into an anti-inflammatory phenotype. Our work provides a powerful strategy for the rational design and development of effective therapies that enhance macrophage-mediated immunotherapy for a variety of diseases.

Original link

ACS Nano ( IF 16 )

Pub Date : 2025-03-28

DOI: 10.1021/acsnano.4c16671

Xuan Mo,  Anping Shen,  Yicun Han,  Li Xu,  Jiaqian Miao,  Danni Xu,  Qing Ji,  Yuelong Cao,  Guangbo Ge,  Xinyuan Zhu,  Hongping Deng