Disruption of dual homeostasis by a metal-organic framework nanoreactor for ferroptosis-based immunotherapy of tumor

• Main Authors: Zhang, Kai, Ma, Zhaoyu, Li, Shuting, Wu, Yang, Zhang, Jin, Zhang, Weiyun, Zhao, Yanli, Han, Heyou
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Chemistry::Biochemistry; Dual Homeostasis; Ferroptosis
• Online Access: https://hdl.handle.net/10356/161844
• Institution: Nanyang Technological University

Ferroptosis, a newfound non-apoptotic cell death pathway that is iron- and reactive oxygen species (ROS)-dependent, has shown a promise for tumor treatment. However, engineering ferroptosis inducers with sufficient hydrogen peroxide (H2O2) and iron supplying capacity remains a great challenge. To address this issue, herein, we report a powerful nanoreactor by modifying MnO2, glucose oxidase, and polyethylene glycol on iron-based metal-organic framework nanoparticles for disrupting redox and iron metabolism homeostasis, directly providing the Fenton reaction-independent downstream ferroptosis for tumor therapy. By consuming glutathione and oxidizing glucose to increase the H2O2 level in cancer cells and downregulating ferroportin 1 to accumulate intracellular iron ions, the homeostasis disruptor could effectively enhance the ferroptosis. Subsequently, the ferroptosis cells release tumor immune-associated antigens, which combine with in situ injected aptamer-PD-L1 to further strengthen the tumor treatment efficiency. This work not only paves a way to enhance the efficacy of ferroptosis-based cancer therapy by associating intracellular redox homeostasis with the iron metabolism system in tumor cells but also offers an engineered nanoreactor as a promising mimetic antigen for activating immunotherapy.