Photocage Prodrug Coupled with Injectable Hydrogel for Self-Amplified Photochemotherapy

Area of Science:

• Biomedical Engineering
• Photopharmacology
• Drug Delivery Systems

Background:

• Developing photocages for photopharmacology is challenging.
• Existing methods often lack spatiotemporal control and exhibit systemic toxicity.

Purpose of the Study:

• To create a photoactivatable photocage prodrug for precise chemotherapy and photodynamic therapy.
• To improve therapeutic selectivity and reduce systemic toxicity of doxorubicin.

Main Methods:

• Synthesized a doxorubicin-methylene blue (DOX-MB) photocage prodrug linked by a urea bond.
• Encapsulated the DOX-MB prodrug into a thermosensitive hydrogel for localized delivery.
• Evaluated in vivo tumor inhibition using 660 nm laser irradiation.

Main Results:

• The DOX-MB photocage demonstrated stability under physiological conditions and quenched fluorescence.
• Laser irradiation triggered urea bond cleavage, releasing active drugs and reactive oxygen species.
• The hydrogel-encapsulated system achieved an 80.3% tumor inhibition rate in vivo.
• Restored methylene blue fluorescence allowed for real-time monitoring.

Conclusions:

• The DOX-MB photocage prodrug enables synergistic photochemotherapy with spatiotemporal control.
• This platform offers a promising strategy for localized tumor therapy with reduced systemic exposure.
• Precision-engineered photoactivatable prodrugs are key for advanced photopharmacology.