Tailorable bimetallic nanozyme mitigates intervertebral disc degeneration by inhibiting oxidative stress and inflammageing.

Rationale: Scavenging reactive oxygen species (ROS), modulating extracellular matrix (ECM) anabolism, and preventing senescence of nucleus pulposus cells (NPCs) are crucial factors of treatment approaches for intervertebral disc degeneration (IDD). However, addressing these issues simultaneously has been challenging due to the interactions among the various pathological factors in the disc microenvironment. Methods: Herein, we utilize self-assembly technology and the excellent drug-carrying potential of mesoporous Prussian blue to design a tailorable bimetallic nanozyme platform of a Mn-modified mesoporous Prussian blue loaded with Cibotium barometz (MPB-Mn3-CB) for the treatment of IDD. Results: The enhancement of multiple antioxidant enzyme activities by MPB-Mn3-CB is ascribed to the lower activation energy of the MnN(4) active site compared to the FeN(4) active site. In vitro and in vivo experiments show that MPB-Mn3-CB efficiently scavenges ROS, promotes ECM synthesis, and rescues the senescent phenotype of NPCs by inhibiting the P53 pathway. Conclusion: This work addresses the specific microenvironmental challenges in severe IDD by synchronously tackling multiple interacting pathological factors and provides a potential therapeutic strategy by multifunctional bimetallic nanozyme for IDD treatment.