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- W4387409402 abstract "Tumor protein 53 (TP53), a key regulator of suppressor genes, is commonly mutated in numerous malignant diseases. Consequently, elimination mutant protein 53 (mutp53) represents an appealing strategy for treating mutp53-related tumors. However, the treatment of these mutations remained challenging due to its formidable limitations. In this study, by loading glucose oxidase (GOX) into Zn-based layered double hydroxides (Zn-LDH) interlayer, a pH-responsive ultrathin nanotherapeutic platform (Zn-LDH@GOX) was created to suppress tumors growth by degrading mutp53. Upon exposure to the acidic environment of lysosomes, the lattice structure of Zn-LDH@GOX was partially disrupted, leading to the release of Zn2+ ions and GOX into the cytoplasm. The increased intracellular concentration of Zn2+ facilitated the restoration of wild-type protein 53 (wtp53) conformation, which in turn degraded mutp53 through activated autophagic pathways. Meanwhile, GOX-induced Heat Shock Protein 90 (HSP90) disruption resulted in the liberation of mutp53 from the HSP90/mutp53 complex and reactivated its degradation via the ubiquitination-mediated proteasomal pathway. In vitro and in vivo experiments confirmed the significant suppression of mutp53 expression and inhibition of tumor growth by Zn-LDH@GOX. Our work offers a novel pH-responsive nanotherapeutic platform with immense potential for mutp53 tumor-specific therapy." @default.
- W4387409402 created "2023-10-07" @default.
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- W4387409402 date "2023-11-01" @default.
- W4387409402 modified "2023-10-11" @default.
- W4387409402 title "An ultrathin Zn-based layered double hydroxides augment degradation of mutant p53 to improve tumor therapy" @default.
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- W4387409402 doi "https://doi.org/10.1016/j.cej.2023.146449" @default.
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