Mated-Atom Nanozymes with Efficient Assisted NAD+ Replenishment for Skin Regeneration

Xiaoyu Liu; Zhen Wan; Ke Chen; Yuxing Yan; Xuyan Li; Yili Wang; Miaoyu Wang; Ruoli Zhao; Jiahui Pei; Lijie Zhang; Si Sun; Jiarong Li; Xinzhu Chen; Qi Xin; Shaofang Zhang; Shuangjie Liu; Hao Wang; Changlong Liu; Xiaoyu Mu; Xiao-Dong Zhang

doi:10.1021/acs.nanolett.4c00546

Mated-Atom Nanozymes with Efficient Assisted NAD⁺ Replenishment for Skin Regeneration

Nano Lett. 2024 Apr 15. doi: 10.1021/acs.nanolett.4c00546. Online ahead of print.

Authors

Xiaoyu Liu^{1

2}, Zhen Wan³, Ke Chen¹, Yuxing Yan¹, Xuyan Li¹, Yili Wang¹, Miaoyu Wang², Ruoli Zhao², Jiahui Pei², Lijie Zhang¹, Si Sun², Jiarong Li², Xinzhu Chen¹, Qi Xin¹, Shaofang Zhang¹, Shuangjie Liu¹, Hao Wang¹, Changlong Liu², Xiaoyu Mu^{1

2}, Xiao-Dong Zhang^{1

2}

Affiliations

¹ Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
² Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin 300350, China.
³ Haihe Hospital, Tianjin University, Tianjin 300350, China.

PMID: 38619329
DOI: 10.1021/acs.nanolett.4c00546

Abstract

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD⁺. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD⁺. Herein, M₁M₂ (M_i=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with K_m-NADH (16.11 μM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD⁺ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.

Keywords: NAD+; NADH oxidase; catalytic selectivity; mated-atom nanozymes; skin regeneration.