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Engineered Multifunctional Zinc-Organic Framework-Based Aggregation-Induced Emission Nanozyme for Accelerating Spinal

Judun Zheng1, Tianjun Chen2, Ke Wang2

  • 1Molecular Diagnosis and Treatment Center for Infectious Diseases, Dermatology Hospital, Southern Medical University, Guangzhou, 510091, P.R. China.

ACS Nano
|January 10, 2024
PubMed
Summary

New nanozymes accelerate spinal cord injury recovery by reducing oxidative stress and inflammation. This zinc-organic framework (Zn@MOF)-based approach aids neural regeneration and promotes motor function restoration in SCI models.

Keywords:
Aggregation-induced emissionNF-κB pathwayOxidative stressSpinal cord injuryZinc−organic framework

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Area of Science:

  • Biomaterials Science
  • Neuroscience
  • Nanotechnology

Background:

  • Spinal cord injury (SCI) functional recovery remains a significant clinical challenge.
  • Current treatments primarily target immune suppression, neglecting crucial oxidative stress pathways.
  • Novel strategies are needed to address the complex pathophysiology of SCI, including oxidative damage and inflammation.

Purpose of the Study:

  • To develop novel zinc-organic framework (Zn@MOF)-based nanozymes for enhanced recovery after spinal cord injury.
  • To investigate the therapeutic potential of these nanozymes in alleviating oxidative stress and promoting neural regeneration.
  • To evaluate the efficacy of the developed nanozymes in a rat model of contusive SCI.

Main Methods:

  • Synthesis of multifunctional Zn@MOF nanozymes (Zn@MOF-TPD) incorporating an aggregation-induced emission-active molecule via bioorthogonal reaction.
  • In situ release of gallic acid and zinc ions (Zn²⁺) at the SCI site.
  • Assessment of nanozyme effects on reactive oxygen species (ROS) scavenging, inflammation, neuronal protection, glial scar inhibition, and neural stem cell proliferation and differentiation.

Main Results:

  • Zn@MOF-TPD nanozymes effectively scavenged ROS, reduced inflammation, and rebalanced the antioxidant defense system.
  • Released Zn²⁺ ions inhibited matrix metalloproteinase 9 (MMP-9) activity, facilitating neuronal regeneration.
  • The nanozymes protected neurons and myelin, inhibited glial scar formation, and promoted neural stem cell activity, leading to improved functional recovery in SCI rats.

Conclusions:

  • Zn@MOF-TPD nanozymes demonstrate significant potential for mitigating oxidative stress-induced damage following SCI.
  • This nanotechnology-based approach effectively promotes neural repair and functional motor recovery.
  • The study highlights a promising therapeutic strategy for addressing the multifaceted challenges of spinal cord injury recovery.