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Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles
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Anti-recurrence/metastasis and chemosensitization therapy with thioredoxin reductase-interfering drug delivery system

Jichun Yang1, Shuojiong Pan2, Shiqian Gao1

  • 1Key Laboratory of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084, China; Tsinghua-Peking Joint Center for Life Sciences, Beijing, 100084, China.

Biomaterials
|April 21, 2020
PubMed

Insights

This study introduces a novel drug delivery system that targets thioredoxin reductase (TrxR) to enhance chemotherapy and prevent cancer recurrence and metastasis. The system releases gemcitabine and inhibits TrxR, inducing apoptosis in residual tumor cells.

Area of Science:

  • Biochemistry
  • Materials Science
  • Oncology

Background:

  • Thioredoxin reductase (TrxR) is crucial in mammalian cells and often overexpressed in cancers, correlating with tumor progression and treatment resistance.
  • TrxR is a promising therapeutic target for anticancer strategies due to its role in tumor survival and metastasis.

Purpose of the Study:

  • To develop a TrxR-interfering drug delivery system (DDS) for gemcitabine (GEM) delivery, aiming to improve chemosensitization and inhibit tumor recurrence and metastasis.
  • To investigate the in vitro and in vivo efficacy of self-assembling micelles that respond to TrxR stimuli.

Main Methods:

  • Fabrication of RGD-PEG-PUSeSe-PEG-RGD self-assembling micelles encapsulating GEM.
  • Utilizing diselenide bonds within the micelles for TrxR-triggered degradation and drug release.
  • Investigating the dynamic Se-Se/Se-S reactions for TrxR activity inhibition and ROS generation.

Main Results:

  • The DDS demonstrated TrxR-responsive GEM release and TrxR activity inhibition.
  • The micelles effectively enhanced gemcitabine chemosensitization against primary tumors.
  • The system reduced tumor recurrence and metastasis by inducing apoptosis in residual cancer cells via ROS production.

Conclusions:

  • The developed TrxR-interfering DDS offers a dual approach for treating primary tumors and preventing post-treatment recurrence and metastasis.
  • This work advances the understanding of selenium biochemistry and the development of new TrxR inhibitors for cancer therapy.
Keywords:
Anti-recurrence/metastasisChemosensitizationDrug delivery systemDynamic covalent chemistryThioredoxin reductase

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