Conditionally Activatable Photoredox Catalysis in Living Systems.

Area of Science:

• Photoredox catalysis
• Biotechnology
• Chemical biology

Background:

• Photoredox catalysis enables novel biological interrogations and biotechnologies.
• Challenges in deploying artificial photoredox catalysis in vivo include photocatalyst toxicity and off-target effects.

Purpose of the Study:

• To develop a conditionally activatable photoredox catalysis (ConAPC) system for safe and effective in vivo applications.
• To design a tumor-specific photoredox catalyst that is activated only at tumor sites.

Main Methods:

• Designed and synthesized the first ConAPC architecture (Se-NO) using self-immolative chemistry to cage photocatalytic activity.
• Identified a new, biologically benign, metal-free photocatalyst (Se-NH) for near-infrared (NIR) photoredox catalysis.
• Evaluated the spatial-temporal control of photoresponsivity in vitro and in vivo, including tumor eradication in a mouse model.

Main Results:

• Achieved potent tumor-specific photocatalytic eradication with a tumor-to-go-interruption (TGI) of 95% in a mouse model.
• Demonstrated high-resolution tumor recognition with a signal-to-background ratio (SBR) of 33.6.
• Confirmed excellent biocompatibility and safety of the ConAPC system.

Conclusions:

• Conditionally activatable photoredox catalysis (ConAPC) provides a viable strategy to overcome photocatalyst toxicity and off-target risks.
• The developed Se-NH photocatalyst enables O2-independent NIR photoredox catalysis for cellular manipulation.
• This work paves the way for developing intelligent photocatalytic theranostics with enhanced safety and efficacy.