MOF-Ag Nanozyme for Fusobacterium nucleatum Eradication and Enhanced Nanocatalytic Therapy of Colorectal Cancer.

PURPOSE: This study aimed to develop a nanocatalytic-microbial therapeutic platform for colorectal cancer (CRC) that simultaneously eliminates the tumor-associated pathobiont Fusobacterium nucleatum (F. nucleatum) and enhances catalytic tumor therapy.

METHODS

An iron-based metal-organic framework (NH2-MIL-88B(Fe) composed of Fe3+ clusters and 2-aminoterephthalic acid, BDC-NH2) loaded with silver nanoparticles (NH2-MIL-88B(Fe)@Ag, denoted as MA) was constructed to integrate antibacterial activity with reactive oxygen species (ROS)-mediated tumor killing. The physicochemical properties, catalytic activity, and antibacterial performance of MA were characterized. Extracellular and intracellular ROS generation, cellular uptake, and cytotoxicity were evaluated in CRC cells. In vivo antitumor efficacy and biosafety were further assessed in a CT26 mouse colon cancer cells (CT26) subcutaneous tumor model with or without F. nucleatum inoculation.

RESULTS

MA exhibited enhanced Fenton-like catalytic activity and generated more hydroxyl radicals than MOF alone in the presence of H2O2, indicating that Ag nanoparticles amplified ROS production. MA also showed potent antibacterial activity against F. nucleatum, enabling concurrent disruption of intratumoral bacteria and tumor cells. In vitro, MA induced pronounced ROS accumulation and significantly reduced CRC cell viability. In vivo, MA markedly suppressed tumor growth, with superior therapeutic efficacy in F. nucleatum-colonized tumors, demonstrating that bacterial elimination contributed substantially to tumor inhibition. No evident systemic toxicity was observed during treatment.

CONCLUSION

MA is a promising nanocatalytic platform for CRC therapy that combines direct antibacterial action against F. nucleatum with amplified ROS-mediated tumor cell killing. This dual-target strategy offers an effective and biocompatible approach for CRC treatment by integrating microbiota intervention with nanocatalytic therapy.