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A fluorescence-activatable tumor-reporting probe for precise photodynamic therapy.

Jian Li1, Tingting Wang2, Feng Jiang1

  • 1State Key Laboratory for Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, and Innovation Center for Cell Signaling Network, Xiamen University, Xiamen 361005, China. shoufa@xmu.edu.cn.

Journal of Materials Chemistry. B
|July 13, 2021
PubMed
Summary

A new trifunctional probe (Glu-RdEB) enables precise photodynamic therapy (PDT) by generating fluorescence at tumor sites. This targeted approach leads to effective tumor regression in mice, highlighting its therapeutic potential.

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Area of Science:

  • Biomedical Engineering
  • Chemical Biology
  • Oncology

Background:

  • Precise photodynamic therapy (PDT) requires targeted approaches for effective tumor treatment.
  • Tumor-specific enzymes offer potential targets for drug activation.
  • Developing activatable probes can enhance therapeutic specificity and reduce side effects.

Purpose of the Study:

  • To develop a trifunctional probe for tumor-specific activation and subsequent photodynamic therapy.
  • To create a probe that generates fluorescence for tumor imaging and a photosensitizer for PDT.
  • To evaluate the probe's efficacy in tumor regression models.

Main Methods:

  • Synthesis of a trifunctional probe (Glu-RdEB) incorporating a GGT-cleavable moiety, a photosensitizer (ENBS), and a quenched fluorophore (rhodamine).
  • In vitro and in vivo studies to assess probe activation by γ-glutamyl transpeptidase (GGT).
  • Evaluation of tumor targeting, fluorescence imaging, and PDT efficacy in a mouse model.

Main Results:

  • The probe (Glu-RdEB) was successfully synthesized and demonstrated GGT-dependent activation.
  • Activated probe released highly fluorescent rhodamine, selectively localized in tumors overexpressing GGT.
  • Light irradiation of tumors treated with the probe resulted in effective tumor regression in mice.

Conclusions:

  • A tumor-activatable fluorescently quenched dye-photosensitizer pair is feasible for precise PDT.
  • The trifunctional probe (Glu-RdEB) enables tumor-specific fluorescence imaging and targeted PDT.
  • This strategy holds promise for improving cancer therapy by enhancing targeting and efficacy.