近年来，癌症免疫疗法是肿瘤治疗中最有希望的方法，其中巨噬细胞在抗肿瘤免疫应答中起到至关重要的作用。然而，肿瘤相关巨噬细胞（TAMs）通常表现为促肿瘤的M2表型，而不是杀伤肿瘤的M1表型。此外，肿瘤细胞上过表达的CD47通过阻断CD47/SIRPα通路严重阻碍了巨噬细胞的功能。在这里，通过超支化氨基化β-环糊精与免疫激活剂咪喹莫德（R848）之间的宿主-客体相互作用，构建了CHTR/siRNA纳米组装体系，而CD47 siRNA则通过静电相互作用被装载在内部。Toll样受体（TLR）7/8激活剂R848能够将巨噬细胞从促肿瘤的M2表型“重新教育”为抗肿瘤的M1表型，而CD47 siRNA能够下调癌细胞表面上的“不要吃我”信号，并增强巨噬细胞对癌细胞的吞噬作用。通过对TAMs的双重调控，减轻了免疫抑制性肿瘤微环境，而宿主-客体药物携带系统对肿瘤产生了协同的免疫疗法效果，抑制了肿瘤生长。纳米药物的简便自组装提供了一种新的策略，可以将多种治疗药物共同运载用于级联癌症免疫疗法。版权所有 © 2023. 由Elsevier B.V.出版。

Cancer immunotherapy is the most promising method for tumor therapy in recent years, among which the macrophages play a critical role in the antitumor immune response. However, tumor-associated macrophages (TAMs) usually display the tumor-promoting M2 phenotype rather than the tumor-killing M1 phenotype. Moreover, the over-expressed CD47 on tumor cells severely hinders the function of macrophages by blocking the CD47/SIRPα pathway. Herein, a nano-assembly system of CHTR/siRNA was constructed through the host-guest interaction of a hyperbranched amino-functionalized β-cyclodextrin and immune agonist imiquimod (R848), while CD47 siRNA was loaded inside through electrostatic interaction. The Toll-like receptor (TLR) 7/8 agonist R848 can "re-educate" macrophages from the protumoral M2 phenotype to antitumoral M1 phenotype, while CD47 siRNA can down-regulate the "don't eat me" CD47 signal on the surface of cancer cells and enhance the phagocytosis of cancer cells by macrophages. Through the dual regulation of TAMs, the immunosuppressive tumor microenvironment was relieved, and the host-guest drug-carrying system resulted in synergistic immunotherapy effect on tumors and inhibited tumor growth. The facile self-assembly of nanodrug offers a new strategy in co-delivery of multiple therapeutic agents for cascade cancer immunotherapy.Copyright © 2023. Published by Elsevier B.V.