Red-light-triggered microenvironment-responsive sustained carbon monoxide release for enhanced tumor therapy

Area of Science:

• Biomedical Engineering
• Cancer Therapeutics
• Drug Delivery Systems

Background:

• Carbon monoxide (CO) shows therapeutic potential in cancer treatment.
• Precise and sustained CO release is essential for efficacy and safety.
• Existing CO delivery methods lack controlled release mechanisms.

Purpose of the Study:

• To develop a light-gated, microenvironment-responsive platform for precise and sustained CO delivery.
• To investigate the platform's efficacy in inducing ferroptosis and inhibiting tumor growth.

Main Methods:

• A CO-releasing platform was constructed using FeCO, tertiary amine (TA) residues, and a Pd-based photosensitizer (PdTPTBP) within a micelle core.
• The platform utilizes light irradiation to trigger initial CO release via H2O2 and GSH.
• A secondary, dark-condition release mechanism was established through a Fenton reaction involving Fe2+ and H2O2.

Main Results:

• The platform demonstrated efficient internalization by 4T1 tumor cells.
• 630 nm light irradiation triggered intracellular CO release, inducing ferroptosis.
• Synergistic disruption of mitochondrial function led to effective antitumor activity in 4T1 tumor-bearing mice.

Conclusions:

• The developed platform enables precise and sustained CO release, controlled by light.
• This CO delivery system effectively induces ferroptosis and exhibits significant antitumor effects.
• The platform holds promise for advanced cancer therapeutic strategies.