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

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

doi:10.1016/j.bioactmat.2024.02.018

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

Bioact Mater. 2024 Feb 21:36:1-13. doi: 10.1016/j.bioactmat.2024.02.018. eCollection 2024 Jun.

Authors

Jianhui Xiang^{1

2}, Xin Yang¹, Manli Tan¹, Jianfeng Guo¹, Yuting Ye¹, Jiejia Deng¹, Zhangrui Huang³, Hanjie Wang³, Wei Su¹, Jianwen Cheng², Li Zheng¹, Sijia Liu¹, Jingping Zhong¹, Jinmin Zhao^{1

3

2}

Affiliations

¹ Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi 530021, PR China.
² Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, PR China.
³ Life Sciences Institute, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, Guangxi, 530021, PR China.

Abstract

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.

Keywords: ATP energy crisis; Nanozymes; Osteoarthritis progression; Oxidative phosphorylation pathway.