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Biodegradable zwitterionic polymer-cloaked defective metal–organic frameworks for ferroptosis-inducing cancer therapy.
- Source :
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International Journal of Pharmaceutics . Apr2024, Vol. 655, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- [Display omitted] • Ferroptosis could effectively kill cancer cells because of their high-loaded reactive oxygen species (ROS), metabolic mutations, and increased requirement for an iron supply. • Ferric metal–organic frameworks (Fe-MOFs) function as nanoplatforms to co-deliver iron ions and a ferroptosis inducer, atorvastatin (ATV), to cancer cells. • The glutathione (GSH)-degradable zwitterionic polymer membrane (PMPC) coated on the surface endowed Fe-MOFs with enhanced stability and long circulation time. • When internalized by cancer cells, these nanoparticles were degraded by GSH, to deplete GSH and release ATV and Fe2+. • The ferroptosis mechanism of this nanoplatform was elucidated. Ferroptosis inhibits tumor growth by iron-dependently accumulating lipid peroxides (LPO) to a lethal extent, which can result from iron overload and glutathione peroxidase 4 (GPX4) inactivation. In this study, we developed biodegradable zwitterionic polymer-cloaked atorvastatin (ATV)-loaded ferric metal–organic frameworks (Fe-MOFs) for cancer treatment. Fe-MOFs served as nanoplatforms to co-deliver ferrous ions and ATV to cancer cells; the zwitterionic polymer membrane extended the circulation time of the nanoparticles and increased their accumulation at tumor sites. In cancer cells, the structure of the Fe-MOFs collapsed in the presence of glutathione (GSH), leading to the depletion of GSH and the release of ATV and Fe2+. The released ATV decreased mevalonate biosynthesis and GSH, resulting in GPX4 attenuation. A large number of reactive oxygen species were generated by the Fe2+-triggered Fenton reaction. This synergistic effect ultimately contributed to a lethal accumulation of LPO, causing cancer cell death. The findings both in vitro and in vivo suggested that this ferroptosis-inducing nanoplatform exhibited enhanced anticancer efficacy and preferable biocompatibility, which could provide a feasible strategy for anticancer therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03785173
- Volume :
- 655
- Database :
- Academic Search Index
- Journal :
- International Journal of Pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 176538764
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2024.124032