A Metal–Organic Framework-Based Immune-Regulating Nanocarrier Depot for Enhanced Combination Cancer Immunotherapy
Tianran Wang, Jiaxuan Yang, Junfeng Ding, Yunan Yuan, Yijun Wu, Jinyuan Zhang, Yan Rong, Yuhao Zhou, Gao Li, Xuesi Chen, Chaoliang He
Abstract
Immunotherapy is a promising cancer treatment with great clinical success. However, its low response rate for many types of cancers is still a limitation owing to the tumor immunosuppressive microenvironment. Herein, an iron-based nanoscale metal–organic framework (MOF) is constructed as a drug carrier with immune-stimulating activity. After reduction and maleimide grafting of basic NH 2 -MIL-88B, the synthesized MOF (rMOF-MA) dramatically increases the production of reactive oxygen species. Accompanied with a high amount of intracellular iron accumulation originating from endocytosis by macrophages, rMOF-MA thus promotes the polarization of macrophages from anti-inflammatory M2 to pro-inflammatory M1 for reprogramming the tumor microenvironment and enhancing immune response. After loading with immune adjuvant resiquimod (R848) and further encapsulation by a tissue-adhesive hydrogel, a local inflammatory niche is constructed. When further combined with immune checkpoint blockade (ICB) therapy, the hydrogel-based combination immunotherapy exhibits strengthened systemic antitumor immunity and significantly inhibits tumor growth, lung metastasis, and tumor recurrence after surgery. Therefore, this MOF-based immune-regulating depot exhibits potential as a promising agent for clinical cancer immunotherapy.