用于重新激活先天细胞，特别是巨噬细胞的靶向免疫调节，有望补充当前的适应性免疫疗法。然而，实体瘤中仍然缺乏阻断巨噬细胞吞噬检查点抑制剂的高性能疗法。本文描述了一种肽-抗体组合超分子原位组装的CD47和CD24双靶点抑制剂（PAC-SABI），它通过配体-受体结合和酶触发反应在癌细胞膜上进行仿生表面传播。通过同时阻断 CD47 和 CD24 信号传导，PAC-SABI 在体外和体内增强巨噬细胞的吞噬能力，​​促进乳腺癌和胰腺癌小鼠模型的抗肿瘤反应。此外，在PAC-SABI诱导巨噬细胞复极化和增加CD8 T细胞肿瘤浸润的基础上，序贯抗PD-1治疗进一步抑制4T1肿瘤进展，延长生存率。基于 PAC-SABI 的纳米结构的体内构建提供了一个有效的平台，用于桥接先天免疫和适应性免疫，以最大限度地提高治疗效力。© 2024。作者。

Targeted immunomodulation for reactivating innate cells, especially macrophages, holds great promise to complement current adaptive immunotherapy. Nevertheless, there is still a lack of high-performance therapeutics for blocking macrophage phagocytosis checkpoint inhibitors in solid tumors. Herein, a peptide-antibody combo-supramolecular in situ assembled CD47 and CD24 bi-target inhibitor (PAC-SABI) is described, which undergoes biomimetic surface propagation on cancer cell membranes through ligand-receptor binding and enzyme-triggered reactions. By simultaneously blocking CD47 and CD24 signaling, PAC-SABI enhances the phagocytic ability of macrophages in vitro and in vivo, promoting anti-tumor responses in breast and pancreatic cancer mouse models. Moreover, building on the foundation of PAC-SABI-induced macrophage repolarization and increased CD8+ T cell tumor infiltration, sequential anti-PD-1 therapy further suppresses 4T1 tumor progression, prolonging survival rate. The in vivo construction of PAC-SABI-based nano-architectonics provides an efficient platform for bridging innate and adaptive immunity to maximize therapeutic potency.© 2024. The Author(s).