MnB-RLG nanozyme ameliorates intervertebral disc degeneration via metabolic-redox modulation

Intervertebral disc degeneration (IDD) is a leading cause of low back pain. Oxidative stress, mitochondrial dysfunction, and lipid peroxidation-driven ferroptosis act as the core pathological drivers, forming a vicious cycle that exacerbates nucleus pulposus cell (NPC) dysfunction and extracellular matrix (ECM) degradation. Conventional therapeutic strategies are limited by single-target intervention and poor clinical efficacy, highlighting the urgent demand for multifunctional nanotherapeutics that synergistically target the complex pathological environment of IDD. Herein, we developed an interfacial electron-regulated manganese boride nanozyme conjugated with resveratrol-lipoic acid-RGD nanomicelles (MnB-RLG), which exhibited multiple enzyme-mimetic activities, including superoxide dismutase (SOD)-like, catalase (CAT)-like and glutathione peroxidase (GPx)-like properties. In vitro experiments revealed that MnB-RLG possessed favorable biocompatibility and efficient cellular internalization capacity, which effectively promoted proliferation and migration of NPCs. Notably, MnB-RLG markedly restrained ferroptosis and enhanced sirtuin 1 (SIRT1)/PTEN induced kinase 1 (PINK1)/Parkin-related mitophagy markers, thereby restoring mitochondrial membrane potential and respiratory capacity, eliminating excessive reactive oxygen species (ROS) accumulation, and maintaining ECM homeostasis in degenerative NPCs. In a rat puncture-induced IDD model, MnB-RLG significantly alleviated disc structural collapse, maintained disc height, and preserved ECM components in vivo. Collectively, this work develops a multifunctional MnB-RLG hybrid nanozyme that exerts synergistic therapeutic effects against IDD through metabolic-redox regulation, providing a potential disease-modifying approach for the clinical management of IDD.