A Multifunctional Covalent Organic Framework Nanozyme for Promoting Ferroptotic Radiotherapy against Esophageal Cancer

Abstract

Radiotherapy is inevitably accompanied by some degree of radiation resistance, which leads to local recurrence and even therapeutic failure. To overcome this limitation, herein, we report the room-temperature synthesis of an iodineand ferrocene-loaded covalent organic framework (COF) nanozyme, termed TADI-COF-Fc, for the enhancement of radiotherapeutic efficacy in the treatment of radioresistant esophageal cancer. The iodine atoms on the COF framework not only exerted a direct effect on radiotherapy, increasing its efficacy by increasing X-ray absorption, but also promoted the radiolysis of water, which increased the production of reactive oxygen species (ROS). In addition, the ferrocene surface decoration disrupted redox homeostasis by increasing the levels of hydroxyl and lipid peroxide radicals and depleting intracellular antioxidants. Both in vitro and in vivo experiments substantiated the excellent radiotherapeutic response of TADI-COF-Fc. This study demonstrates the potential of COF-based multinanozymes as radiosensitizers and suggests a possible treatment integration strategy for combination oncotherapy.

Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy

“…[201] (B) Ferrocene-modified TADI-COF-Fc as a multifunctional nanozyme for boosting ferroptotic radiotherapy. [203] ferrocene units (Figure 14B). The iodine atoms on the COF scaffold increased the X-ray deposition, thereby causing an elevated degree of DNA damage.…”

“…Besides phototherapy, radiotherapy can also be optimized by using COF nanozymes that destroy inherent radioresistance. In 2023, Dong et al [203] designed TADI-COF-Fc, a COF multienzyme containing iodine atoms and (A) Cu(II)-coordinated COF-909-Cu with SOD-, POD-, and GPX-mimicking activity for inducing pyroptosis. [201] (B) Ferrocene-modified TADI-COF-Fc as a multifunctional nanozyme for boosting ferroptotic radiotherapy.…”

“…(A) Cu(II)-coordinated COF-909-Cu with SOD-, POD-, and GPX-mimicking activity for inducing pyroptosis [201]. (B) Ferrocene-modified TADI-COF-Fc as a multifunctional nanozyme for boosting ferroptotic radiotherapy [203].…”

Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy

“…[201] (B) Ferrocene-modified TADI-COF-Fc as a multifunctional nanozyme for boosting ferroptotic radiotherapy. [203] Angewandte Chemie Aufsätze ferrocene units (Figure 14B). The iodine atoms on the COF scaffold increased the X-ray deposition, thereby causing an elevated degree of DNA damage.…”

Symmetrical Localized Built-in Electric Field by Induced Polarization Effect in Ionic Covalent Organic Frameworks for Selective Imaging and Killing Bacteria

“…Among photocatalysis materials (g-C 3 N 4 , MoS 2 , Fe 3 O 4 , and so on), , covalent organic frameworks (COFs) can adjust organic building blocks by covalent or coordinated bonds to achieve the different structures. COFs can precisely assemble different molecular species into two- or three-dimensional (2D or 3D) structures. , The adjustable topology structures endow COFs with special characteristics, including porous structures, abundant active sites, and excellent electronic properties, which have attracted enormous attention on photocatalysis, sensors, and energy storage. − However, COFs always exhibit limited efficiency for charge separation and photocatalytic performance due to the strong exciton binding energy. ,− The microscopic structures and electronic structure of materials play a crucial role in electron transfer, such as morphology, the size of particles, heterostructure, and so on. − The design of the COF structure provides more possibility to improve the utilization of photogenerated carriers.…”