Atomic Artificial Enzyme for Acute and Chronic Pneumonia.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Immunology

Background:

• Pneumonia presents complex immunological challenges with limited effective treatments.
• Natural enzymes offer therapeutic potential for oxidative stress but face limitations in stability and cost.
• Gold nanoclusters (Au NCs) are explored as stable, bioactive artificial enzymes for lung injury.

Purpose of the Study:

• To investigate the potential of gold nanoclusters (Au NCs) as next-generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD).
• To evaluate the enzymatic activity, stability, and therapeutic efficacy of Au NCs in preclinical models of lung inflammation.

Main Methods:

• Synthesis and characterization of gold nanoclusters (Au NCs), specifically Au25 and Au24Er1.
• In vitro evaluation of Au NCs' catalase (CAT) and glutathione peroxidase (GPx) mimetic activity.
• Assessment of Au NCs' effects on mitochondrial oxidative stress and adenosine triphosphate (ATP) synthesis.
• In vivo studies using mouse models of acute lung injury (ALI) and ovalbumin-induced allergic lung disease (ALD).
• Analysis of molecular mechanisms including the TLR4/MyD88/NF-κB pathway and macrophage polarization.

Main Results:

• Au NCs demonstrated significant catalase and glutathione peroxidase-like activity, with Au24Er1 showing a higher affinity for H2O2 than natural CAT.
• Au NCs effectively inhibited mitochondrial oxidative stress and promoted ATP synthesis.
• Treatment with Au NCs suppressed the TLR4/MyD88/NF-κB pathway and M1 macrophage response in ALI.
• Au NCs rescued the Th1/Th2 imbalance in an allergic lung disease model.
• Lung function was notably improved in both ALI and ALD models following Au NC treatment.

Conclusions:

• Gold nanoclusters (Au NCs) exhibit potent anti-inflammatory and antioxidant properties, making them effective in preclinical models of lung injury.
• Au NCs serve as a viable alternative to natural enzymes, offering enhanced stability and potential for treating various lung diseases, including pneumonia.
• These findings highlight Au NCs as promising biopharmaceuticals for immunomodulation and therapeutic intervention in lung injury.