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Doxorubicin prodrug for γ-glutamyl transpeptidase imaging and on-demand cancer therapy

  • 0College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan, 250014, PR China.
Biosensors & Bioelectronics +

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January 8, 2025

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January 8, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study developed a novel doxorubicin (Dox) prodrug that targets liver cancer by responding to γ-glutamyl transpeptidase (γ-GGT). This approach enables integrated diagnosis and treatment, improving chemotherapy safety and efficacy.

Area Of Science

  • Oncology
  • Biomedical Engineering
  • Drug Delivery

Background

  • γ-glutamyl transpeptidase (γ-GGT) is a key biomarker for liver cancer progression.
  • Targeted drug delivery systems are crucial for enhancing chemotherapy efficacy and reducing side effects.
  • Developing responsive prodrugs offers a strategy for on-demand cancer treatment.

Purpose Of The Study

  • To design and synthesize a doxorubicin (Dox) prodrug responsive to γ-GGT for liver cancer imaging and treatment.
  • To create a nano-prodrug by encapsulating the Dox prodrug in hyaluronic acid-modified liposomes for enhanced tumor targeting.
  • To evaluate the efficacy of the nano-prodrug, in combination with anti-PD-L1 therapy, in inhibiting tumor growth.

Main Methods

  • Synthesis of a γ-GGT-cleavable doxorubicin prodrug.
  • Formulation of hyaluronic acid-modified liposome nanoparticles encapsulating the doxorubicin prodrug (nano-prodrug).
  • In vitro and in vivo evaluation of the nano-prodrug's targeting ability, drug release profile, and anti-tumor efficacy, including combination therapy with anti-PD-L1.

Main Results

  • The γ-GGT-responsive doxorubicin prodrug successfully released free doxorubicin in the presence of γ-GGT.
  • The nano-prodrug exhibited enhanced accumulation in tumors due to CD44 receptor targeting.
  • Combination therapy with anti-PD-L1 significantly inhibited both proximal and distal tumor growth, demonstrating synergistic effects.

Conclusions

  • The developed γ-GGT-responsive nano-prodrug offers a promising strategy for targeted liver cancer therapy.
  • This integrated approach allows for imaging of γ-GGT levels and on-demand drug release, improving treatment precision.
  • The combination with anti-PD-L1 immunotherapy enhances anti-tumor activity, highlighting its potential in clinical applications.

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