Min Tao, Yang Chunzheng, Zhang Minghui, Hu Ping, Shi Jianlin
Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai, 200050, P. R. China.
Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200331, P. R. China.
Small. 2024 Dec 8:e2407734. doi: 10.1002/smll.202407734.
Malignant pleural effusion (MPE) is one of the most difficult complications of cancer to cure, usually indicating poor prognosis in late-stage cancer patients. Due to the presence of a large number of tumor-associated immune cells with the tumor promoting phenotype in MPE and pleural tumors, current clinical therapy offers limited effectiveness. Here, a mild magnetothermal regulation strategy is proposed based on a magnetic nanocatlytic nanoplatform ZCMF@PEG-AF (ZCMF-AF) constructed by surface-modifying anti-F4/80 antibody (AF) on ZnCoFeO@ZnMnFeO magnetic nanoparticles (ZCMF) to target and polarize tumor-associated macrophages. Under alternating magnetic field-induced hyperthermia (41-42 °C), ZCMF-AF exhibits in situ nanocatalytic production of hydroxyl radicals via released iron ions under acidic cellular environment, which induces repolarization from the immunosuppressed M2 phenotype to the M1 phenotype. More importantly, the tumor cell damage induced by M1 macrophages and magnetic hyperthermia promote the maturation of dendritic cells, which subsequently awakens cytotoxic T lymphocytes to combat tumor cells. The integrated innate and adaptive immunity activations based on ZCMF-AF nano-immunomedicine through intrapleural administration elicit substantially regulated immune microenvironment of MPE and pleural tumors. Moreover, the interpleural magnetic nanoparticle-based immunotherapy effectively reduced the MPE volume and inhibited tumor growth in the pleural cavity, significantly prolonging the survival of the MPE-bearing mice.
恶性胸腔积液（MPE）是癌症最难治愈的并发症之一，通常表明晚期癌症患者预后不良。由于MPE和胸膜肿瘤中存在大量具有促肿瘤表型的肿瘤相关免疫细胞，目前的临床治疗效果有限。在此，基于在ZnCoFeO@ZnMnFeO磁性纳米颗粒（ZCMF）表面修饰抗F4/80抗体（AF）构建的磁性纳米催化纳米平台ZCMF@PEG-AF（ZCMF-AF），提出了一种温和的磁热调节策略，以靶向并极化肿瘤相关巨噬细胞。在交变磁场诱导的热疗（41-42°C）下，ZCMF-AF在酸性细胞环境中通过释放铁离子原位纳米催化产生羟基自由基，从而诱导免疫抑制的M2表型重新极化至M1表型。更重要的是，M1巨噬细胞和磁热疗诱导的肿瘤细胞损伤促进了树突状细胞的成熟，随后唤醒细胞毒性T淋巴细胞对抗肿瘤细胞。通过胸膜内给药基于ZCMF-AF纳米免疫药物的固有免疫和适应性免疫激活可显著调节MPE和胸膜肿瘤的免疫微环境。此外，基于胸膜间磁性纳米颗粒的免疫疗法有效减少了MPE体积并抑制了胸腔内肿瘤生长，显著延长了荷MPE小鼠的生存期。
