NIR-enhanced Pt single atom/g-C<sub>3</sub>N<sub>4</sub> nanozymes as SOD/CAT mimics to rescue ATP energy crisis by regulating oxidative phosphorylation pathway for delaying osteoarthritis progression.

Xiang, Jianhui; Yang, Xin; Tan, Manli; Guo, Jianfeng; Ye, Yuting; Deng, Jiejia; Huang, Zhangrui; Wang, Hanjie et al. · Bioact Mater · 2024

basic_science · Level V

Where this comes from

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 Pt<sup>4+</sup> with modified g-C<sub>3</sub>N<sub>4</sub> by π-π interaction to prepare g-C<sub>3</sub>N<sub>4</sub>-loaded Pt single-atom (Pt SA/C<sub>3</sub>N<sub>4</sub>) 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/C<sub>3</sub>N<sub>4</sub> 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-N<sub>6</sub> active centres in Pt SA/C<sub>3</sub>N<sub>4</sub> formed electron capture sites for electron holes, in which g-C<sub>3</sub>N<sub>4</sub> 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-C<sub>3</sub>N<sub>4</sub> and g-C<sub>3</sub>N<sub>4</sub>-loaded Pt nanoparticles (Pt NPs/C<sub>3</sub>N<sub>4</sub>). Based on the use of H<sub>2</sub>O<sub>2</sub>-induced chondrocytes to simulate ROS-injured cartilage <i>in</i><i>vitro</i> and an OA joint model <i>in</i><i>vivo</i>, the results showed that Pt SA/C<sub>3</sub>N<sub>4</sub> 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/C<sub>3</sub>N<sub>4</sub> could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C<sub>3</sub>N<sub>4</sub> 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.