Unveiling the active sites on ferrihydrite with apparent catalase-like activity for potentiating radiotherapy. (December 2021)

• Record Type: Journal Article
• Authors: Zhang, Ruofei; Chen, Lei; Liang, Qian; Xi, Juqun; Zhao, Hanqing; Jin, Yiliang; Gao, Xingfa; Yan, Xiyun; Gao, Lizeng; Fan, Kelong
• Is Part Of: Nano today. Volume 41(2021)
• Publication Date: 2021-12
• Subjects: Catalase -- Ferrihydrite -- Structure-activity relationship -- Hypoxia -- Nanozyme -- Radiotherapy; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2021.101317
• Languages: English
• ISSNs: 1748-0132

Abstract

Highlights: Ferrihydrite was found to exhibit catalase-like activity superior to other iron oxides. The surface iron-associated hydroxyl groups were found to act as the catalytic sites of ferrihydrite. Ferrihydrite catalase nanozyme does not possess peroxidase-like, oxidase-like or superoxide dismutase-like activities. The effect of ferrihydrites as catalase-like nanozymes to sensitize radiotherapy was evaluated in vitro and in vivo . The biosafety and biodegradability of ferrihydrite were analyzed. Graphical Abstract: ga1 Abstract: The use of catalase-like nanozymes in relieving tumor hypoxia has been a promising strategy for adjuvant radiotherapy, yet their catalytic mechanism and toxic potential remain elusive. While most studies on catalase-like mechanisms focus on the substrates and products in the catalytic process, little is reported to analyze the dominating surface structure for catalytic activity of nanozymes. Here, we reported the catalase-like activity of ferrihydrite and revealed its structure-activity relationship. Among the ten main forms of iron oxide nanomaterials, ferrihydrite, especially 2-line ferrihydrite, exhibited the highest catalase-like activity. Importantly, the structure-activity fitting and density functional analysis revealed that the abundant surface iron-associated hydroxyl groups dominantly affect the catalase-like activity of ferrihydrites. In addition, the ferrihydrite exhibited no peroxidase-like and superoxide dismutase-like activities, and constantly catalyzed the decomposition of H2 O2 to release O2 in the pH range of 4.0–8.7. With the help of steady and single catalase-like activity in the physiological environment, ferrihydrite safely and effectively catalyzed the H2 O2 in tumor microenvironment to in-situ produce O2 and significantly enhanced the therapeutic effect of radiotherapy. Moreover, ferrihydrite exhibited excellent biosafety and biodegradability. These findings demonstrate the great potential of ferrihydrite as a biocompatible catalase-like nanozyme for relieving hypoxia in cancer therapy.