Iron-based metal-organic framework co-loaded with buthionine sulfoximine and oxaliplatin for enhanced cancer chemo-ferrotherapy via sustainable glutathione elimination Article Swipe
Zhiping Rao
,
Yutian Xia
,
Qian Jia
,
Yutong Zhu
,
Lexuan Wang
,
Guohuan Liu
,
Xuelan Liu
,
Peng Yang
,
Pengbo Ning
,
Ruili Zhang
,
Xianghan Zhang
,
Chaoqiang Qiao
,
Zhongliang Wang
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1186/s12951-023-01998-w
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1186/s12951-023-01998-w
Background Emerging ferroptosis-driven therapies based on nanotechnology function either by increasing intracellular iron level or suppressing glutathione peroxidase 4 (GPX4) activity. Nevertheless, the therapeutic strategy of simultaneous iron delivery and GPX4 inhibition remains challenging and has significant scope for improvement. Moreover, current nanomedicine studies mainly use disulfide-thiol exchange to deplete glutathione (GSH) for GPX4 inactivation, which is unsatisfactory because of the compensatory effect of continuous GSH synthesis. Methods In this study, we design a two-in-one ferroptosis-inducing nanoplatform using iron-based metal-organic framework (MOF) that combines iron supply and GPX4 deactivation by loading the small molecule buthionine sulfoxide amine (BSO) to block de novo GSH biosynthesis, which can achieve sustainable GSH elimination and dual ferroptosis amplification. A coated lipid bilayer (L) can increase the stability of the nanoparticles and a modified tumor-homing peptide comprising arginine-glycine-aspartic acid (RGD/R) can achieve tumor-specific therapies. Moreover, as a decrease in GSH can alleviate resistance of cancer cells to chemotherapy drugs, oxaliplatin (OXA) was also loaded to obtain BSO&OXA@MOF-LR for enhanced cancer chemo-ferrotherapy in vivo. Results BSO&OXA@MOF-LR shows a robust tumor suppression effect and significantly improved the survival rate in 4T1 tumor xenograft mice, indicating a combined effect of dual amplified ferroptosis and GSH elimination sensitized apoptosis. Conclusion BSO&OXA@MOF-LR is proven to be an efficient ferroptosis/apoptosis hybrid anti-cancer agent. This study is of great significance for the clinical development of novel drugs based on ferroptosis and apoptosis for enhanced cancer chemo-ferrotherapy. Graphical Abstract
Related Topics
Concepts
Buthionine sulfoximine
Oxaliplatin
Glutathione
Chemistry
Metal-organic framework
Metal
Cancer
Cancer research
Colorectal cancer
Biochemistry
Internal medicine
Organic chemistry
Medicine
Enzyme
Adsorption
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s12951-023-01998-w
- https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-023-01998-w
- OA Status
- gold
- Cited By
- 30
- References
- 33
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385738222
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4385738222Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1186/s12951-023-01998-wDigital Object Identifier
- Title
-
Iron-based metal-organic framework co-loaded with buthionine sulfoximine and oxaliplatin for enhanced cancer chemo-ferrotherapy via sustainable glutathione eliminationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-08-10Full publication date if available
- Authors
-
Zhiping Rao, Yutian Xia, Qian Jia, Yutong Zhu, Lexuan Wang, Guohuan Liu, Xuelan Liu, Peng Yang, Pengbo Ning, Ruili Zhang, Xianghan Zhang, Chaoqiang Qiao, Zhongliang WangList of authors in order
- Landing page
-
https://doi.org/10.1186/s12951-023-01998-wPublisher landing page
- PDF URL
-
https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-023-01998-wDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-023-01998-wDirect OA link when available
- Concepts
-
Buthionine sulfoximine, Oxaliplatin, Glutathione, Chemistry, Metal-organic framework, Metal, Cancer, Cancer research, Colorectal cancer, Biochemistry, Internal medicine, Organic chemistry, Medicine, Enzyme, AdsorptionTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
30Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 11, 2024: 19Per-year citation counts (last 5 years)
- References (count)
-
33Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.(OXA) | 156 |
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