Dual metabolic targeting liposomes potentiate triple-negative breast cancer radiosensitivity via glucose and glutathione starvation
Abstract
Triple-negative breast cancer (TNBC) frequently develops resistance to radiotherapy, while its metabolic reliance on glucose and glutamine presents new therapeutic targets for radiotherapy sensitization. This study developed a targeted nanoliposome (G/B-Lip-R) co-delivering glucose oxidase (GOD) and buthionine sulfoximine (BSO) to enhance radiotherapy through dual metabolic intervention. GOD catalyzes glucose oxidation to generate hydrogen peroxide (H 2 O 2) while depleting tumor energy supplies, whereas BSO inhibits glutathione (GSH) synthesis to disrupt redox homeostasis. Their synergistic action significantly elevates intracellular reactive oxygen species (ROS) levels, thereby potentiating radiosensitivity. Both in vitro and in vivo studies demonstrated that G/B-Lip-R effectively targets tumors and significantly improves radiotherapy outcomes. This work innovatively combines nanocarriers with dual metabolic pathway modulation, offering a novel strategy to overcome TNBC radioresistance with important clinical translation potential.
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Additional strategies included depletion of intracellular glutathione and modulation of redox balance, as well as metabolic interventions targeting glycolysis or cellular energetics.
“Additional strategies included depletion of intracellular glutathione (GSH) and modulation of redox balance [17,19,45,47,68], as well as metabolic interventions targeting glycolysis or cellular energetics [49,69,75,76].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [76]
The most consistent antitumor effects were observed with integrated nanoplatforms combining high-atomic-number-mediated dose amplification with catalytic ROS generation, redox modulation, hypoxia targeting, drug delivery, or immune-modulating strategies.
“While many studies demonstrated increased ROS generation and DNA damage following nanoparticle-assisted irradiation, the most consistent antitumor effects were observed with integrated nanoplatforms combining high-atomic-number–mediated dose amplification with catalytic ROS generation, redox modulation, hypoxia targeting, drug delivery, or immune-modulating strategies [17,21,23,39,40,45,52,68,76,7”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [76]
Major differences in nanoparticle composition, particle size, surface functionalization, therapeutic payloads, irradiation protocols, experimental models, and outcome assessment methods substantially complicate direct cross-study comparison and limit quantitative synthesis.
“Major differences in nanoparticle composition, particle size, surface functionalization, therapeutic payloads, irradiation protocols, experimental models, and outcome assessment methods [15,20,24,33,37,45,52,68,76,81] substantially complicate direct cross-study comparison and limit quantitative synthesis.”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [76]
The translational feasibility of complex integrated nanoplatforms remains uncertain because biodistribution, pharmacokinetics, long-term toxicity, immunogenicity, manufacturing scalability, and regulatory reproducibility were infrequently evaluated.
“While these systems often demonstrated strong preclinical efficacy [17,21,23,39,40,45,52,68,76,77], their translational feasibility remains uncertain because biodistribution, pharmacokinetics, long-term toxicity, immunogenicity, manufacturing scalability, and regulatory reproducibility were infrequently evaluated [10,11,13,16,93,94,95,96,97,98,99,100,102].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [76]
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“While these systems often demonstrated strong preclinical efficacy [17,21,23,39,40,45,52,68,76,77], their translational feasibility remains uncertain because biodistribution, pharmacokinetics, long-term toxicity, immunogenicity, manufacturing scalability, and regulatory reproducibility were…”
InfluentialLigand-functionalized liposomal vesicles in breast cancer: advances in targeted nanotherapeutics
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- Authors
- Zhang, H., Liu, Y., Gao, X., Ji, G., Zheng, Y., Luo, F., Qi, X., Zhao, S., Guan, S., Wang, C., & Lu, M.
- Affiliations
- Shandong University (CN)
- Tongji University (CN)
- Corresponding author
- Lu, Ming
- Venue
- Nanomedicine: Nanotechnology, Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2025-11
- Volume
- 70
- Pages
- 102870
- ISSN
- 1549-9634 (ISSN-L)
- OpenAlex
- W4415339688
- Cited by
- 3
- References
- 27
- Citations by year
- 2026: 3
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nanomedicine Nanotechnology Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82403788)
- Shandong Province Natural Science Foundation (ZR2025MS1194)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Keywords
- triple-negative breast cancer, radiosensitization, radioresistance (biology), glucose oxidase, buthionine sulfoximine, liposomes, glucose deprivation, glutathione synthesis inhibition, reactive oxygen species, hydrogen peroxide, metabolic targeting, glutamine metabolism, redox homeostasis
- MeSH terms
- Animals, Female, Glucose, Glucose Oxidase, Glutathione, Humans, Liposomes, Radiation Tolerance, Reactive Oxygen Species, Buthionine Sulfoximine, Cell Line, Tumor, Mice, Triple Negative Breast Neoplasms
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