Glutathione-Depleted Photodynamic Nanoadjuvant for Triggering Nonferrous Ferroptosis to Amplify Radiotherapy of Breast Cancer
Abstract
Radiotherapy plays a crucial role in the treatment of advanced breast cancer, but the increased antioxidant system, especially the rise in glutathione (GSH), presents a significant obstacle to its effectiveness. To address this challenge, a versatile GSH-depleted photodynamic nanoadjuvant is developed to augment the efficacy of radiotherapy for breast cancer treatment. This nanoadjuvant operates within the tumor microenvironment to effectively deplete intracellular GSH through a sequence of cascaded processes, including GSH exhaustion, biosynthetic inhibition, and photodynamic oxidation. This leads to a notable accumulation of lipid peroxides (LPO) and subsequent suppression of glutathione peroxidase 4 (GPX4) activity. Consequently, the combined GSH depletion induced by the nanoadjuvant markedly promotes nonferrous ferroptosis, thereby contributing to the augmentation of antitumor efficiency during radiotherapy in breast cancer. This work presents an innovative approach to designing and synthesizing biocompatible nanoadjuvants with the goal of improving the efficacy of radiotherapy for breast cancer in prospective clinical scenarios.
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Ferroptosis was reported in several studies, particularly in association with redox modulation and glutathione depletion.
“Ferroptosis was reported in several studies, particularly in association with redox modulation and glutathione depletion [15,17,68,77,78], while additional pathways such as pyroptosis were also described [16,39].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [78]
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- Authors
- Shi, J., Cui, G., Jin, Y., Mi, B., Liu, K., Zhao, L., Bao, K., Lu, Z., Liu, J., Wang, Y., He, H., & Guo, Z.
- Affiliations
- Soochow University (CN)
- Suzhou University of Science and Technology (CN)
- Corresponding author
- He, Hui
- Guo, Zhengqing
- Venue
- Advanced Healthcare Materials
- Publisher
- Wiley
- Published
- 2024-10-13
- Volume
- 13
- Issue
- 31
- Pages
- e2402474-e2402474
- ISSN
- 2192-2640 (ISSN-L)
- 2192-2659
- OpenAlex
- W4403376719
- Cited by
- 18
- References
- 58
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 1
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Healthcare Materials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (32171383, 31971298, 31771089)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Keywords
- glutathione depletion, photodynamic therapy, nanoparticle adjuvants, breast cancer, radiotherapy enhancement, lipid peroxidation, GPX4, antioxidant defense, tumor microenvironment
- MeSH terms
- Ferroptosis, Phospholipid Hydroperoxide Glutathione Peroxidase, Animals, Breast Neoplasms, Female, Glutathione, Humans, Mice, Inbred BALB C, Photochemotherapy, Cell Line, Tumor, Mice, Nanoparticles, Tumor Microenvironment
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