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Related Concept Videos

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Related Experiment Video

Updated: Jan 21, 2026

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
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ROS-responsive self-immolative polymeric prodrug for nitrosative stress-mediated cancer therapy.

Anup Dey1, Jeongjin Lee1, Minsung Park2

  • 1School of Chemical Engineering, College of Engineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Jangan-gu, Suwon 16419, Republic of Korea.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|January 19, 2026
PubMed
Summary
This summary is machine-generated.

This study introduces a novel polymer prodrug that releases nitric oxide (NO) and scavenges glutathione in tumors. This targeted approach shows potent anticancer effects and minimal toxicity, offering a new redox-responsive therapy.

Keywords:
Cancer treatmentGlutathione depletionNitric oxidePolymeric prodrugReactive oxygen speciesSelf-immolative polymer

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Production and Detection of Reactive Oxygen Species ROS in Cancers
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Area of Science:

  • Biomedical Engineering
  • Cancer Therapeutics
  • Drug Delivery Systems

Background:

  • Nitric oxide (NO) is a promising redox regulator for cancer therapy.
  • Conventional NO donors face limitations due to short half-lives and poor tumor specificity.
  • Reactive oxygen species (ROS) are elevated in the tumor microenvironment, presenting a therapeutic target.

Purpose of the Study:

  • To develop a ROS-responsive, self-immolative polymeric prodrug (G-g-PSIP) for targeted cancer therapy.
  • To investigate the prodrug's mechanism of action, including NO release, glutathione scavenging, and ROS responsiveness.
  • To evaluate the antitumor efficacy and safety of G-g-PSIP in vitro and in vivo.

Main Methods:

  • Synthesis and characterization of the G-g-PSIP polymeric prodrug.
  • In vitro cytotoxicity assays using CT26 cancer cells and L929 normal cells.
  • Assessment of intracellular glutathione depletion, NO generation, and peroxynitrite formation.
  • In vivo antitumor efficacy studies in CT26 tumor-bearing mice.

Main Results:

  • G-g-PSIP demonstrated dose-dependent cytotoxicity against CT26 cancer cells with minimal toxicity to normal cells.
  • The prodrug effectively scavenged glutathione and generated NO in response to elevated ROS.
  • Cascade-amplified depolymerization led to peroxynitrite accumulation, inducing nitrosative stress and ferroptosis-like cell death.
  • Systemic administration of G-g-PSIP achieved significant antitumor efficacy in vivo.

Conclusions:

  • G-g-PSIP is a potent ROS-responsive polymeric prodrug for targeted cancer therapy.
  • The synergistic effects of GSH depletion and NO/peroxynitrite generation induce ferroptosis-like cell death.
  • This redox-responsive platform holds promise for developing novel cancer treatments.