Chemical insights on covalent organic frameworks for ferroptosis and pyroptosis in cancer

Abstract

Covalent organic frameworks (COFs), with their customizable structures and properties, can be employed as comprehensive platforms for drug delivery and generating reactive oxygen species (ROS). This Tutorial Review outlines practical guidelines for the design, synthesis, and engineering of COFs to achieve oxidative-stress-driven cell death, with a focus on ferroptosis and the emerging pyroptosis pathways. It discusses COF customization to overcome antioxidative barriers, deliver redox-active species, release the abundant ROS, and optimize the therapeutic efficacy, while minimizing adverse effects. The chemical design and mechanism of the COF are comprehensively discussed, within the context of the biological redox environment and oxidative damage leading to ferroptosis or pyroptosis. Furthermore, this review explores strategies for enhancing the specificity and therapeutic effects of ferroptosis and pyroptosis induction in potential synergy with conventional cancer treatments. The challenges and perspectives associated with translating COF-based therapies have also been addressed. Overall, COFs represent a versatile platform for targeted ferroptosis and pyroptosis induction in cancer therapy, offering insights into the future of precision medicine and personalized cancer therapy.