Covalent organic frameworks for ferroptosis cancer therapy

Ferroptosis offers a promising potential for effective cancer therapy, promoting Fenton reaction-mediated lipid peroxidation to induce cell death; moreover, the implementation of ferroptosis can overcome the previous issue of drug resistance associated with conventional treatments. Covalent organic frameworks (COFs) are organic materials that exhibit crystallinity, porosity, surface functionality, drug delivery, and biocompatibility. This review discusses the unique functionalities of COFs, including framework, nanopore, surface area, and surface functionalizability, which effectively induce ferroptosis in cancer therapy while minimizing side effects on healthy tissues. To the best of our knowledge, this represents the first review to focus on the COFs for ferroptosis-based cancer therapy. This review also describes a synergistic combination of the COFs and ferroptosis-inductive molecular delivery. Furthermore, we highlight the potential of combinatorial ferroptosis cancer therapy, which can be effectively achieved by utilizing the multifunctionality of COFs, thereby synergizing with photodynamic therapy, photothermal therapy, chemodynamic therapy, sonodynamic therapy, radiotherapy, and immunotherapy. Ultimately, we discuss the challenges associated with scalability, biocompatibility, cancer-specific targetability, effective delivery, stimulus responsiveness, and multifunctionality of the COFs that need to be overcome to fully utilize unique advantages of the COFs in the clinics.