A context-aware artificial metabzyme in intervertebral disc degeneration metabolic convergence therapy

Hypoxia-driven dysregulated lactate metabolism is a feature of intervertebral disc degeneration (IDD). However, biological metabzymes and most biomimetic counterparts are ineffective under hypoxic conditions and often generate harmful metabolites. Here, a single-atom nanozyme is presented that exhibits catalytic activity rivaling a biological metabzyme and pathological context-aware metabolism functions within the male rats’ disc microenvironment, termed the “biogenic Fe-N-C artificial metabzyme”. The spatially dynamic metabolomics and assessments of IDD tissues demonstrate that biogenic Fe-N-C artificial metabzyme efficiently catalyzes the conversion of excess lactate into pyruvate and reduced glutathione within IDD. Subsequent metabolic convergence of mitochondria and extracellular matrix coordinates the recovery of the internal and external nucleus pulposus cells environment, constituting IDD metabolic therapy. The current work proves that creating artificial metabzymes tailored to the pathological tissue environment can be used to correct metabolic dysfunction. Hypoxia-driven dysregulated lactate metabolism is a feature of intervertebral disc degeneration (IDD), but biological metabzymes and most biomimetic counterparts are ineffective under hypoxic conditions and often yield harmful metabolites. Here, the authors report a biogenic Fe-N-C artificial metabzyme for IDD metabolic therapy that reprograms lactate metabolism and corrects metabolic dysfunction.