Antioxidant Nanotherapies for Intervertebral Disk Degeneration: Progress and Prospects

Intervertebral disk degeneration (IVDD) is widely recognized as a major contributor to discogenic low back pain (LBP), imposing a substantial burden on global public health and socioeconomic systems. Growing evidence confirms that disrupted redox homeostasis, excessive reactive oxygen species (ROS) accumulation, and oxidative stress act as major convergent mechanisms that propagate inflammatory cascades, nucleus pulposus cell dysfunction, and extracellular matrix degradation. Although conventional conservative therapies and surgical interventions are clinically effective in relieving macrostructural compression, they remain limited in resolving localized molecular dysregulation. In recent years, nanotechnology has emerged as a promising strategy for overcoming the limitations of traditional therapy for IVDD. This review provides an analysis of four categories of antioxidant nanotherapies for IVDD, including inorganic functional nanozymes, bioactive nanomaterials, stimuli-responsive nanosystems, and nanocomposite scaffolds. We elaborate on their mechanisms in scavenging excessive ROS, restoring redox equilibrium, protecting mitochondrial function, and ameliorating oxidative stress-induced degeneration. Integrating structural biomimicry with microenvironmental responsiveness enables the engineering of composite nanosystems with multi-pathway ROS-scavenging capabilities. Therefore, these platforms emerge as promising therapeutic strategies for arresting IVDD progression. Finally, we discuss the key obstacles to clinical translation. Overall, this review provides insights into the development of redox-targeted therapies.