Click and Release: A High-Content Bioorthogonal Prodrug with Multiple Outputs

Area of Science:

• Chemical Biology
• Drug Delivery
• Bioorthogonal Chemistry

Background:

• Bioorthogonal chemistry enables precise molecular modifications within biological systems.
• Multimodal therapy requires simultaneous delivery of multiple therapeutic agents.
• Prodrug strategies enhance drug targeting and reduce systemic toxicity.

Purpose of the Study:

• To develop a high-content bioorthogonal prodrug with multiple outputs.
• To establish proof of concept for co-delivery of a gasotransmitter, anticancer drug, and fluorescent reporter.
• To enable real-time monitoring of prodrug activation.

Main Methods:

• Design and synthesis of a "click, cyclize, and release" bioorthogonal prodrug.
• Co-delivery of carbon monoxide (gasotransmitter), floxuridine (anticancer drug), and a fluorescent reporter.
• In situ generation of a fluorescent reporter for real-time monitoring.

Main Results:

• Successful demonstration of the "click, cyclize, and release" mechanism.
• Co-delivery of carbon monoxide and floxuridine achieved.
• Real-time monitoring of prodrug activation via in situ fluorescence confirmed.

Conclusions:

• Bioorthogonal prodrugs are effective tools for multimodal therapy.
• The developed prodrug system allows for simultaneous delivery and real-time monitoring.
• This platform holds significant potential for advancing cancer treatment strategies.