An Orally Defect-Rich MoO_3-x Nanozyme Enhances ROS Scavenging for Inflammatory Bowel Disease Therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gastroenterology

Background:

• Inflammatory bowel disease (IBD) presents therapeutic challenges due to excessive reactive oxygen species (ROS) and lack of targeted treatments.
• Current strategies often struggle with efficacy and targeted delivery for gastrointestinal inflammation.

Purpose of the Study:

• To develop ultrasmall, defect-rich MoO3-x nanozymes for enhanced ROS scavenging in IBD treatment.
• To evaluate the therapeutic potential and safety of these nanozymes for oral delivery in an IBD model.

Main Methods:

• Fabrication of ultrasmall MoO3-x nanozymes via liquid-phase synthesis.
• In vitro assessment of ROS scavenging, antioxidant activities (catalase, SOD-like, hydroxyl radical), and stability in gastric conditions.
• In vivo evaluation in a murine IBD model, including assessment of colonic inflammation, MPO activity, gut microbiota composition (16S rRNA sequencing), and systemic exposure.

Main Results:

• The synthesized MoO3-x nanozymes exhibited significant ROS scavenging capabilities, superior to non-catalytic antioxidants.
• Optimized nanozymes (MoO3-x (-200)) demonstrated stability for oral delivery and effectively alleviated colonic inflammation in mice.
• Treatment reduced proinflammatory factors and myeloperoxidase activity, with no significant systemic exposure observed.
• Gut microbiota analysis indicated a partial modulation of microbial composition, favoring beneficial bacteria.

Conclusions:

• Ultrasmall, defect-rich MoO3-x nanozymes are promising therapeutic agents for inflammatory bowel disease due to their ROS scavenging and anti-inflammatory properties.
• These nanozymes offer a stable oral formulation with potential to modulate gut microbiota, providing a novel approach for IBD treatment.