Dual-targeted N-PMI^plus@CA nanoplatform for concurrent MDM2 and β-catenin inhibition in p53 wild-type lung adenocarcinoma.

ABSTRACT: Lung adenocarcinoma (LUAD) harboring wild-type p53 remains therapeutically challenging because of the oncogenic MDM2-driven suppression of p53 activity and compensatory activation of Wnt/β-catenin signaling. Here, we report a self-assembled nanoparticle system (N-PMI^plus@CA) enabling simultaneous inhibition of both MDM2 and the Wnt/β-catenin pathway. We observed that concurrent activation of these two pathways is significantly correlated with poor clinical outcomes in patients with LUAD. N-PMI^plus@CA efficiently accumulated in tumor tissues via enhanced permeability and retention (EPR) effects and macropinocytosis, delivering both an optimized MDM2-inhibitory peptide and a β-catenin antagonist (carnosic acid). The dual-inhibition strategy significantly restored p53 fu

SUBMITTER: Zhao N 

PROVIDER: S-EPMC12320182 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature