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A dual-modal GSH depletion and NIR-triggered nanoplatform for cascade-amplified phototherapy

Shuang Liu1, Xingyu Chen1, Xiaojin Liu2

  • 1School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China.

Colloids and Surfaces. B, Biointerfaces
|January 22, 2026
PubMed

Insights

This study developed a novel nanoplatform that depletes glutathione (GSH) and uses near-infrared light to combine photodynamic therapy (PDT) and photothermal therapy (PTT) for enhanced tumor treatment with minimal toxicity.

Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Oncology

Background:

  • Intracellular glutathione (GSH) and low reactive oxygen species (ROS) generation hinder phototherapy efficacy in tumors.
  • Developing strategies to overcome tumor antioxidant defenses is crucial for effective cancer treatment.

Purpose of the Study:

  • To construct a dual-modal nanoplatform for enhanced photothermal therapy (PTT) and photodynamic therapy (PDT).
  • To create a nanoplatform that depletes GSH and is triggered by near-infrared (NIR) light for synergistic tumor eradication.

Main Methods:

  • A nanoplatform (Ce6@CDP) was engineered with a copper sulfide (CuS) core and a disulfide bond-containing polymer (DS-ANPA-PEG) encapsulating Ce6.
  • The polymer reacts with intracellular GSH, leading to GSH depletion and increased oxidative stress.
  • CuS core facilitates NIR-triggered PTT, while Ce6 enables PDT, creating a combined therapeutic effect.

Main Results:

  • The nanoplatform effectively depleted GSH and generated ROS, significantly enhancing PDT efficacy.
  • High photothermal conversion efficiency of the CuS core enabled potent PTT under 808 nm laser irradiation.
  • In vitro and in vivo studies confirmed significant tumor growth inhibition with negligible systemic toxicity.

Conclusions:

  • The developed nanoplatform offers a promising strategy for synergistic PDT/PTT by overcoming tumor antioxidant defenses.
  • This GSH-depleting, NIR-triggered system provides a rational design for responsive multimodal nanotherapeutics.
  • The approach shows potential for effective and safe cancer treatment through combined therapeutic modalities.
Keywords:
Glutathione depletionNanoplatformPhotodynamic therapyPhotothermal therapyTumor combination therapy

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