Nanoscale Metal-Organic Frameworks-Mediated Degradation of Mutant p53 Proteins and Activation of cGAS-STING Pathway for Enhanced Cancer Immunotherapy.

ABSTRACT: Activating cGAS-STING pathway has great potential to achieve effective antitumor immunotherapy. However, mutant p53 (mutp53), a commonly observed genetic alteration in over 50% of human cancer, will impede the therapeutic performance of the cGAS-STING pathway. Herein, multifunctional ZIF-8@MnO₂ nanoparticles are constructed to degrade mutp53 and facilitate the cGAS-STING pathway. The synthesized ZIF-8@MnO₂ can release Zn²⁺ and Mn²⁺ in cancer cells to induce oxidative stress and cytoplasmic leakage of fragmented mitochondrial double-stranded DNAs (dsDNAs). Importantly, the released Zn²⁺ induces variable degradation of multifarious p53 mutants through proteasome ubiquitination, which can alleviate the inhibitory effects of mutp53 on the

SUBMITTER: Sun L 

PROVIDER: S-EPMC10966556 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature