Precision-Architected Drug-Stabilized Cu₅ Clusters Mediate Multimodal Therapeutic Intervention in Colitis

Area of Science:

• Nanotechnology
• Materials Science
• Biomedical Engineering

Background:

• Atomically precise metal clusters offer potential for drug delivery due to their unique properties.
• Developing effective treatments for inflammatory bowel diseases like colitis remains a significant challenge.

Purpose of the Study:

• To fabricate an anti-inflammatory agent-stabilized copper cluster (Cu5) for multimodal therapy against colitis.
• To investigate the efficacy of the Cu5 cluster in alleviating colitis in a mouse model.

Main Methods:

• Conjugation of propargylated drugs to a Cu5 cluster using specific bridging modes.
• Evaluation of gastrointestinal stability, antioxidant capability, and anti-inflammatory effects of the Cu5 cluster in vitro and in vivo.
• Assessment of the Cu5 cluster's impact on reactive oxygen nitrogen species, macrophage repolarization, intestinal barrier restoration, and gut microbiota.

Main Results:

• The Cu5 cluster demonstrated remarkable gastrointestinal stability and antioxidant capacity.
• Oral administration of the Cu5 cluster effectively scavenged reactive oxygen nitrogen species and attenuated inflammation in inflamed colon sites.
• The positively charged Cu5 cluster inhibited pathogenic bacteria, restored gut microbiota diversity, and significantly alleviated dextran sulfate sodium-induced colitis in mice.

Conclusions:

• The developed Cu5 cluster serves as a promising multifunctional platform for colitis treatment.
• This work provides a paradigm for designing advanced metal clusters for therapeutic applications and drug delivery.