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Compartmentalized Nanozyme-Enzyme Cascade Enables Metabolic-Redox Coupling for Acute Kidney Injury Therapy
Yujing Tang1, Mingyue Shi1, Yuting Guo1
1School of Chemical Science and Engineering, Tongji University, Shanghai200092, China.
Nano Letters
|August 12, 2026
Summary
This study introduces UL-Gel, a novel nanozyme-enzyme system that simultaneously reduces lactate and reactive oxygen species to treat acute kidney injury (AKI). UL-Gel effectively restores kidney function by targeting coupled metabolic and oxidative pathways.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Renal Medicine
Background:
- Acute kidney injury (AKI) involves complex metabolic dysfunction and oxidative stress.
- Current AKI treatments often lack efficacy due to the multifactorial nature of the disease.
- Synergistic therapeutic strategies are needed to address coupled pathological pathways in AKI.
Purpose of the Study:
- To design and develop a core-shell nanozyme-metabolic enzyme cascade microreactor, named UL-Gel.
- To investigate the synergistic effects of lactate depletion and reactive oxygen species scavenging for AKI treatment.
- To explore UL-Gel's therapeutic potential in a preclinical AKI model.
Main Methods:
- Enzyme-driven interfacial radical gelation to construct the UL-Gel system.
- Utilizing lactate oxidase, UIO-66, catalase, and superoxide dismutase activities within the microreactor.
- Employing an established animal model of acute kidney injury for in vivo evaluation.
- Assessing renal lactate levels, endogenous antioxidant enzyme activities, and transcriptomic profiles.
Main Results:
- UL-Gel demonstrated effective synergistic lactate depletion (69.3% reduction) and reactive oxygen species scavenging in the AKI model.
- Treatment with UL-Gel restored endogenous antioxidant enzyme activities in the kidneys.
- Transcriptomic analysis revealed that UL-Gel modulated key signaling pathways, including AGE-RAGE-NOX4 and PI3K-Akt, indicating renal landscape restoration.
Conclusions:
- UL-Gel represents a promising smart therapeutic platform for complex metabolic diseases like AKI.
- The integration of dynamic nanozyme kinetics and material engineering offers a novel approach for synergistic treatment.
- This study highlights the potential of multi-target interventions for recalcitrant pathologies.
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