癌症免疫疗法正在发展成为癌症治疗的主流策略。然而，程序性细胞死亡蛋白1（PD-1）和程序性死亡配体1（PD-L1）之间的相互作用限制T细胞增殖，导致肿瘤细胞的免疫逃逸。近年来，免疫检查点抑制剂疗法通过阻断PD-1/PD-L1检查点通路在肿瘤治疗中取得了临床成功。然而，肿瘤微环境（TME）中M2肿瘤相关巨噬细胞（TAM）的存在会抑制抗肿瘤免疫反应并促进肿瘤生长，从而削弱免疫检查点抑制剂治疗的有效性。 M2 TAM 复极化为 M1 TAM 可以诱导免疫反应，分泌促炎因子和活性 T 细胞攻击肿瘤细胞。在此，制备了中空氧化铁 (Fe3O4) 纳米颗粒 (NP)，用于将 M2 TAM 重编程为 M1 TAM。 BMS-202是一种小分子PD-1/PD-L1抑制剂，与抗体相比具有更低的价格、更高的稳定性、更低的免疫原性和更高的肿瘤穿透能力，将pH敏感的NaHCO3负载在空心Fe3O4纳米颗粒中，然后用巨噬细胞膜包裹。形成的仿生FBN@M可以响应酸性TME而从NaHCO3产生气态二氧化碳（CO2），破坏巨噬细胞膜以释放BMS-202。一系列体外和体内评估表明，FBN@M可以将M2 TAM重编程为M1 TAM并阻断PD-1/PD-L1通路，最终诱导T细胞活化以及TNF-α和IFN-γ的分泌以杀死肿瘤细胞。 FBN@M 对肿瘤治疗显示出显着的免疫治疗功效。

Cancer immunotherapy is developing as the mainstream strategy for treatment of cancer. However, the interaction between the programmed cell death protein-1 (PD-1) and the programmed death ligand 1 (PD-L1) restricts T cell proliferation, resulting in the immune escape of tumor cells. Recently, immune checkpoint inhibitor therapy has achieved clinical success in tumor treatment through blocking the PD-1/PD-L1 checkpoint pathway. However, the presence of M2 tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) will inhibit antitumor immune responses and facilitate tumor growth, which can weaken the effectiveness of immune checkpoint inhibitor therapy. The repolarization of M2 TAMs into M1 TAMs can induce the immune response to secrete proinflammatory factors and active T cells to attack tumor cells. Herein, hollow iron oxide (Fe3O4) nanoparticles (NPs) were prepared for reprogramming M2 TAMs into M1 TAMs. BMS-202, a small-molecule PD-1/PD-L1 inhibitor that has a lower price, higher stability, lower immunogenicity, and higher tumor penetration ability compared with antibodies, was loaded together with pH-sensitive NaHCO3 inside hollow Fe3O4 NPs, followed by wrapping with macrophage membranes. The formed biomimetic FBN@M could produce gaseous carbon dioxide (CO2) from NaHCO3 in response to the acidic TME, breaking up the macrophage membranes to release BMS-202. A series of in vitro and in vivo assessments revealed that FBN@M could reprogram M2 TAMs into M1 TAMs and block the PD-1/PD-L1 pathway, which eventually induced T cell activation and the secretion of TNF-α and IFN-γ to kill the tumor cells. FBN@M has shown a significant immunotherapeutic efficacy for tumor treatment.