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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月5日

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  • Lei Li,
  • Wei Deng,
  • Siyuan Chen,
  • Qiujiang Li,
  • Xuanyu Xiao,
  • Linyu Long,
  • Yuanyuan Xu,
  • Yuting Zhong,
  • Dan Song,
  • Jingyi Yang,
  • Tianshu Wang,
  • Ganjun Feng,
  • Yunbing Wang

摘要

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.