Iron (II)-based metal-organic framework nanozyme for boosting tumor ferroptosis through inhibiting DNA damage repair and system Xc.
J Nanobiotechnology
; 22(1): 228, 2024 May 08.
Article
en En
| MEDLINE
| ID: mdl-38715049
ABSTRACT
Development of ferroptosis-inducible nanoplatforms with high efficiency and specificity is highly needed and challenging in tumor ferrotherapy. Here, we demonstrate highly effective tumor ferrotherapy using iron (II)-based metal-organic framework (FessMOF) nanoparticles, assembled from disulfide bonds and ferrous ions. The as-prepared FessMOF nanoparticles exhibit peroxidase-like activity and pH/glutathione-dependent degradability, which enables tumor-responsive catalytic therapy and glutathione depletion by the thiol/disulfide exchange to suppress glutathione peroxidase 4, respectively. Upon PEGylation and Actinomycin D (ActD) loading, the resulting FessMOF/ActD-PEG nanoplatform induces marked DNA damage and lipid peroxidation. Concurrently, we found that ActD can inhibit Xc- system and elicit ferritinophagy, which further boosts the ferrotherapeutic efficacy of the FessMOF/ActD-PEG. In vivo experiments demonstrate that our fabricated nanoplatform presents excellent biocompatibility and a high tumor inhibition rate of 91.89%.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño del ADN
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Estructuras Metalorgánicas
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Ferroptosis
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Hierro
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article