基于生物正交反应的 M1 巨噬细胞靶向及抗肿瘤效应增强

Chimeric antigen receptor macrophages (CAR-Ms), which are genetically engineered, have application prospects in solid tumor therapy because of the prominent role of macrophages in the tumor microenvironment. Recently, non-natural sugar metabolic labeling based on bioorthogonal reactions has emerged as a research hotspot in targeted tumor therapy.

In this study, 4T1 cells and M1 macrophages were incubated with Ac 4 GalBCN and Ac 4 ManNAz, respectively, to equip the cell surfaces with -BCN and -N 3 groups. These modifications enhanced the proximity between these two kinds of cells and promoted phagocytosis and cytokine release.

Moreover, compared to other groups, the bioorthogonal labeling group exhibited heightened tumor-targeted effects and antitumor phagocytic activity against 4T1 cells in vivo. Addition of the small-molecule inhibitor RRx-001 further improved the synergistic effect on phagocytosis and immune cell phenotypes in tumors.

In summary, our study highlights the metabolic labeling strategy as a potent approach to promote M1 macrophage-mediated antitumor responses within the tumor environment, providing a novel means for the development of therapeutic strategies tailored for solid tumors.