Journal Article

NIR-enhanced Pt single atom/g-C3N4 nanozymes as SOD/CAT mimics to rescue ATP energy crisis by regulating oxidative phosphorylation pathway for delaying osteoarthritis progression

Yang, Xin, Tan, Manli, Ye, Yuting, Wang, Hanjie, Zhao, Jinmin, Su, Wei, Huang, Zhangrui, Deng, Jiejia, Zheng, Li, Zhong, Jingping, Liu, Sijia, Xiang, Jianhui, Cheng, Jianwen, Guo, Jianfeng

2024

Overview

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π–π interaction to prepare g–C3N4–loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt–N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g–C3N4–loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage invitro and an OA joint model invivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases. •Design of a ligand-mediated strategy for nanozyme preparation.•Tunable enzymatic activity under NIR light irradiation to scavenge ROS/RNS.•Density Functional Theory study on the SOD/CAT-like catalytic mechanism of Pt SA/C3N4 nanozymes.•Regulation of the expression of mitochondrial respiratory chain complexes.

• Publisher: Elsevier B.V,KeAi Publishing Communications Ltd,KeAi Publishing,KeAi Communications Co., Ltd
• Subject: Adsorption / Apoptosis / Arthritis / ATP energy crisis / ATP synthase / Beta decay / Carbon nitride / Cartilage / Cartilage diseases / Catalase / Catalytic converters / Chondrocytes / Damage / Electron capture / Electron transport / Electrons / Energy metabolism / Energy shortages / Free radicals / Holes (electron deficiencies) / Hydrogen peroxide / I.R. radiation / Inflammatory diseases / Ligands / Light irradiation / Metabolism / Microenvironments / Mitochondria / Nanoparticles / Nanozymes / Near infrared radiation / Nitrogen / Osteoarthritis / Osteoarthritis progression / Oxidative metabolism / Oxidative phosphorylation / Oxidative phosphorylation pathway / Oxidative stress / Phosphorylation / Photothermal conversion / Reactive nitrogen species / Reactive oxygen species / Superoxide dismutase