Structurally Engineered Ferrous Metal-Organic Framework as a Chemodynamic Therapy Nanoagent for Concurrent Hydroxyl...

Area of Science:

• Nanotechnology
• Materials Science
• Biomedical Engineering

Background:

• Chemodynamic therapy (CDT) uses nanoagents to convert hydrogen peroxide into cytotoxic hydroxyl radicals (•OH).
• Current CDT agents generate either •OH or singlet oxygen (¹O₂), but not both, limiting efficacy.
• Existing nanoplatforms often have suboptimal catalytic activity, hindering sufficient reactive oxygen species (ROS) production.

Purpose of the Study:

• To develop a novel nanoagent for enhanced chemodynamic therapy.
• To create a single platform capable of simultaneously generating both •OH and ¹O₂.
• To investigate the therapeutic efficacy and safety of the new nanoagent in cancer treatment.

Main Methods:

• Synthesis of a ferrous metal-organic framework, Fe(II)-TCPP, with nanoneedle morphology.
• In vitro studies using cancer cells to assess intracellular ROS generation and cytotoxicity.
• In vivo studies in a breast cancer mouse model to evaluate tumor accumulation, ROS production, therapeutic effect, and systemic toxicity.

Main Results:

• Fe(II)-TCPP demonstrated dual catalytic activity, generating both •OH and ¹O₂ simultaneously via Fenton-like and Russell mechanisms.
• Selective intracellular ROS generation in cancer cells led to targeted cytotoxicity.
• Fe(II)-TCPP accumulated in tumors, eradicated cancer, and prevented recurrence in mice without systemic toxicity.

Conclusions:

• Fe(II)-TCPP is the first nanoagent to integrate Fenton and Russell mechanisms for dual ROS generation in CDT.
• The nanoneedle morphology and dual catalytic pathways enhance ROS output and therapeutic efficacy.
• This foundational advance enables the design of multifunctional nanoagents for improved cancer treatment with reduced toxicity.