Construct an “immunogenic cell death” amplifier based on Fe-MOFs by accelerating Fe(iii) reduction strategies for integration of tumor diagnosis, treatment, and prevention

Abstract

Traditional tumor treatments focus on treating the location of the lesion, while immunogenic cell death (ICD) triggers systemic anti-tumor immunity and inhibits tumor metastasis. Therefore, there is a need to develop an inducer that amplifies ICD. Here, methotrexate (MTX) and MoO₂ were loaded into a Cu²⁺-doped iron-based targeted metal–organic framework Fe–NH₂-MIL-101 with nano-enzymatic activity to establish a novel ICD amplifier. The photothermal agent MoO₂ generates heat under near-infrared (NIR) light excitation, inducing tumor ablation. Simultaneously, the released Mo⁺ combines with Fe²⁺ and Cu⁺ in the system, synergistically enhancing electron transfer efficiency based on the bimetallic system. Combined with thermal effects, this approach cooperatively elevates glutathione peroxidase (GPx)-like and peroxidase (POD)-like activities. This catalytic cascade depletes glutathione through Fenton-like reactions while amplifying hydroxyl radical (˙OH) generation, thereby remodeling the tumor microenvironment (TME), potentiating chemodynamic therapy (CDT), and triggering ICD. The chemotherapeutic agent MTX not only exerts direct cytotoxic effects but also serves as an inducer of ICD. In vitro and in vivo experiments have shown that the resulting synergistic treatment model based on the combination of CDT, photothermal therapy (PTT), and chemotherapy guided by T₂-MRI imaging will amplify the ICD effect, enhance tumor treatment, and is expected to achieve the prevention of metastasis and recurrence of tumors and to realize the integration of tumor diagnosis, treatment, and prevention.