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April 11, 2026Advanced Composites and Hybrid MaterialsOpen Access

Hypoxia nanoalleviator with dual disruption of iron and redox metabolism for efficient ferroptosis-mediated cancer immunotherapy

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Authors

WYWeimin YinTongji UniversityYLYang LiTongji UniversitySCShiyu ChenFujian Normal University

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Implication

Demonstrates improved ferroptosis and immune response in tumors with novel treatment approach, suggesting potential benefits in cancer therapy.

Key Points

  • To develop a hypoxia nanoalleviator that disrupts iron and redox metabolism for enhanced ferroptosis in cancer immunotherapy.
  • Designed a hypoxia nanoalleviator co-loaded with CaO2 and glutaminase inhibitor C968 on nanocarriers.
  • Under acidic conditions, CaO2 generates O2 and H2O2 to alleviate hypoxia.
  • HMOX1 expression is upregulated, catalyzing heme to release Fe2+ and downregulating SLC40A1.
  • Induces a Fenton-like reaction between Fe2+ and H2O2 to produce reactive oxygen species (ROS).
  • Inhibits glutamate transporter SLC1A1, reducing glutathione production and enhancing ROS.
  • Significant accumulation of intracellular Fe2+ occurs due to disrupted iron homeostasis.
  • Enhanced ROS production leads to effective ferroptosis triggering immunogenic cell death.
  • T-cell immune responses are activated, resulting in robust tumor growth and metastasis suppression.

Cite This Study

Yin et al. (2026) studied this question.

synapsesocial.com/papers/69d9e58f78050d08c1b75d55https://doi.org/10.1007/s42114-026-01734-6
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