Advanced Functional Materials, 6 December, 2020, DOI：https://doi.org/10.1002/adfm.202007130

Inositol Polyphosphate Multikinase Inhibits Liquid-Liquid Phase Separation of TFEB to Negatively Regulate Autophagy Activity

Juqun Xi Ruofei Zhang Liming Wang Wei Xu Qian Liang Jingyun Li Jian Jiang Yili Yang Xiyun Yan Kelong Fan Lizeng Gao

Abstract

Artificial peroxisome has drawn a lot of attentions for its usefulness in fabricating protocell system and great potential in treating diseases. However, it is still a significant challenge to prepare a practicable artificial peroxisome to complement multiple and stable functions under physiological condition. Herein, a novel strategy is reported to design an artificial peroxisome using a nanozyme to accommodate multiple enzyme‐like activities that mimics those enzymes in natural peroxisome. The enzymatic active sites are introduced into graphitized moieties on the shell of a hollow carbon nanozyme by doping iron and nitrogen to form Fe–N₄ coordination and atomic Fe cluster. With Fe clusters as reversible cofactors and Fe–N₄ as prosthetic group, the resulted carbon nanozyme exhibits stable and multiple peroxisomal‐like activities, including catalase, uricase, superoxide dismutase, peroxidase, and oxidase, which is referred as nanozyme‐based artificial peroxisome (pero‐nanozysome). This pero‐nanozysome shows therapeutic effect for treating hyperuricemia and protecting neurons from free radicals generated during ischemic stroke by employing the tandem activities of uricase‐catalase and superoxide‐dismutase‐catalase, respectively. This study indicates that the pero‐nanozysome is a promising candidate to design artificial peroxisome performing in vivo functions.

Artilce link：https://onlinelibrary.wiley.com/doi/10.1002/adfm.202007130