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Updated: Apr 23, 2026

Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
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Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ

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A Deep-Red-Absorbing Osmium(II)-Based Photosensitizer Evokes Pyroptosis by Targeting Glutamine Metabolism and

Yiyi Zhang1, Zhimei Xiao1, James W Southwell1

  • 1Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005 Paris, France.

Journal of the American Chemical Society
|April 21, 2026
PubMed

Insights

Researchers developed a new strategy to induce pyroptosis, a form of programmed cell death, in cancer cells. This method reprograms cancer cell metabolism, enhancing antitumor immunity and offering a new approach for cancer immunotherapy.

Area of Science:

  • Biochemistry
  • Immunology
  • Materials Science

Background:

  • Pyroptosis is an emerging target in cancer immunotherapy.
  • Current pyroptosis-inducing compounds are often discovered serendipitously.

Purpose of the Study:

  • To develop a novel pyroptosis-inducing strategy via metabolic reprogramming.
  • To enhance antitumor immunity using a targeted approach.

Main Methods:

  • Constructed an osmium-based photosensitizer-inhibitor conjugate (Os-IMD).
  • Utilized a glutamine carrier protein inhibitor (IMD-0354) for targeted delivery.
  • Investigated the effects of Os-IMD on cancer cell metabolism and cell death pathways.

Main Results:

  • Os-IMD enhanced photosensitizer uptake via the glutamine metabolic pathway.
  • Os-IMD inhibited glutamine uptake and promoted mitochondrial targeting.
  • Light irradiation of Os-IMD induced gasdermin D (GSDMD)-mediated pyroptosis, switching from apoptosis.

Conclusions:

  • Metabolic reprogramming offers a scalable strategy for pyroptosis induction.
  • Os-IMD effectively induces pyroptosis through mitochondrial damage and redox imbalance.
  • This approach provides a new avenue for developing pyroptosis-inducing agents for cancer immunotherapy.

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