Design of Monovalent Cerium-Based Metal Organic Frameworks as Bioinspired Superoxide Dismutase Mimics for Ionizing Radiation Protection

Abstract

Superoxide dismutase (SOD) is one of the major antioxidants in vivo and is expected to play critical roles on the defense against reactive oxygen species (ROS)-mediated damages, such as ionizing radiation damages. Herein, inspired by the function and structure of natural SODs and cerium oxide nanozymes, two monovalent cerium-based metal organic frameworks (Ce-MOFs), CeIIIBTC and CeIVBTC, were designed for superoxide radical (O2 •–) elimination and ionizing radiation protection. These two Ce-MOFs selectively scavenge O2 •– and are excellent SOD mimics. Like natural SODs and cerium oxide nanozymes, the SOD-like catalytic mechanism of Ce-MOFs involves a cycle between Ce(IV) and Ce(III). Furthermore, by constructing monovalent Ce-MOFs, we found that high-valent CeIVBTC are more effective SOD-like nanozymes compared to CeIIIBTC. With smaller size, better monodispersity, and more effective SOD-like activity, CeIVBTC nanozymes were further applied for ionizing radiation protection. Both in vitro and in vivo results demonstrated that CeIVBTC nanozymes could efficiently scavenge ROS, prevent cells from γ-ray radiation-induced cell viability decrease and DNA damages, and improve the survival rate of irradiated mice by recovering the bone marrow DNA damage and alleviating oxidative stress of tissues. The protective effect and good biocompatibility of CeIVBTC nanozymes will enable the development of Ce-MOFs-based radioprotectants and facilitate treatment of other ROS-related diseases.

Air-Derived Inhibitor of Nanozymes

“…34−37 We first chose Ce-MOF-808 NPs as our study model, which were fabricated as reported. 38 As shown in Figure 1c, the experimental Ce-MOF-808 NPs exhibited an irregular morphology. The X-ray diffraction (XRD) pattern of the experimental Ce-MOF-808 NPs corresponded well to the simulated MOF-808, which indicated the successful synthesis of Ce-MOF-808 NPs (Figure 1d).…”

“…As expected, the activity of alkaline phosphatase decreased with increasing concentrations of added HPO 4 2– (Figure S1). Ce 6 cluster-based MOF (Ce-MOF) NPs are well known for their alkaline phosphatase-mimicking activities, and Ce 6 clusters serve as catalytic active centers. − We first chose Ce-MOF-808 NPs as our study model, which were fabricated as reported . As shown in Figure c, the experimental Ce-MOF-808 NPs exhibited an irregular morphology.…”

“…Fabrication of Ce-MOF NPs. For Ce-MOF-808 NPs, in a typical procedure, 38 (NH 4 ) 2 Ce(NO 3 ) 6 (470 mg) was dissolved in 1.6 mL of water in a 50 mL flask. The solution was heated at 100 °C in an oil bath for 5 min under stirring, followed by the introduction of 5.85 mL of acetic acid.…”

Enzyodynamic therapy at nanoscale

“…Ce-MOFs Superoxide dismutase CHO cells [54] PB@MSCM Oxidase Hematopoietic cells [55] F I G U R E 1 Schematic illustration of enzyodynamic therapy (EDT) at nanoscale for representative nanozyme paradigms, advantages of EDT and versatile biomedical applications, including ROS-producing EDT and ROS-scavenging EDT. Created by BioRender.…”

“…One of the main mechanisms of radiation damage effect is the free radical damage, because the radiation decomposition of biological molecules is the main chemical pathway to produce free radicals. 54 Free radicals not only play an important role in the process of acute radiation disease, but also continue to cause tissue damage during the acute phase following the latent phase. Research shows that the free radicals produced by radiation, especially ROS, are one of the main causes of damage.…”