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Photocage Prodrug Coupled with Injectable Hydrogel for Self-Amplified Photochemotherapy.

Yingjian Cui1, Jianxin Rong1, Xiaoya Wu1

  • 1Institute of Polymer Science and Engineering, School of Chemical Engineering, Hebei University of Technology, Tianjin 300130, China.

Journal of Medicinal Chemistry
|June 26, 2026
PubMed
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This study introduces a novel photocage prodrug (DOX-MB) for precise cancer treatment. This photoactivatable system enables targeted chemotherapy and photodynamic therapy, significantly reducing systemic toxicity and improving tumor inhibition rates.

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:

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  • 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.