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Updated: Feb 14, 2026

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Simultaneous Down-Regulation of Intracellular hTERT and GPX4 mRNA Using MnO2-Nanosheet Probes to Induce Cancer Cell

Yixin Miao1, Tao Zhou1, Qinghong Ji1

  • 1School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China.

Sensors (Basel, Switzerland)
|February 13, 2026
PubMed

Insights

This study introduces a novel manganese dioxide nanosheet probe that delivers gene therapy to target cancer cells. The nanotherapy effectively suppresses tumor growth by simultaneously down-regulating key cancer genes and depleting glutathione.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Cancer poses a significant global health challenge, with conventional therapies facing limitations in efficacy and tolerability.
  • Gene therapy and nanodrug delivery represent emerging strategies for precision oncology.
  • Overexpression of human telomerase reverse transcriptase (hTERT) and glutathione peroxidase 4 (GPX4) is implicated in cancer progression and resistance to cell death.

Purpose of the Study:

  • To develop a multifunctional nanoplatform for synergistic cancer treatment.
  • To co-deliver antisense oligonucleotides targeting hTERT and GPX4 mRNA using manganese dioxide nanosheets (MnO2-NS).
  • To investigate the combined effects of gene silencing and glutathione depletion on cancer cell death.

Main Methods:

  • Fabrication of MnO2-NS probes loaded with fluorescently labeled antisense oligonucleotides against hTERT and GPX4 mRNA.
  • Demonstration of glutathione (GSH)-responsive release of antisense oligonucleotides.
  • Assessment of cellular uptake, gene silencing efficacy, and induction of apoptosis and ferroptosis in cancer cell lines.
  • Evaluation of antitumor efficacy in vitro compared to single-target or carrier-only controls.

Main Results:

  • The MnO2-NS probe demonstrated efficient cellular uptake and controlled release of antisense oligonucleotides in the presence of GSH.
  • Co-delivery of antisense oligonucleotides significantly suppressed cancer cell proliferation.
  • Molecular analyses confirmed successful down-regulation of hTERT and GPX4 expression.
  • The treatment led to GSH depletion, increased reactive oxygen species (ROS) accumulation, and enhanced lipid peroxidation, promoting synergistic cancer cell death.

Conclusions:

  • The developed MnO2-NS-based co-delivery system effectively achieves synergistic gene silencing and GSH depletion.
  • This multifunctional nanotherapy enhances antitumor efficacy by inducing dual cell death pathways.
  • The study presents a promising nanotherapeutic strategy for precision oncology.
Keywords:
GPX4gene silencinghTERTinhibiting cancer cell proliferationmanganese dioxide nanosheet probe

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