Targeting CAD with a tumor microenvironment-responsive nano-heterojunction for synergistic induction of cuproptosis and inhibition of colorectal cancer progression.

ABSTRACT: Carbamoyl-phosphate synthetase II/Aspartate transcarbamylase/Dihydroorotase (CAD) is a multifunctional enzyme with demonstrated oncogenic potential across various cancers, emerging as a promising therapeutic target. However, its functional role and therapeutic relevance in colorectal cancer (CRC) remain unclear. Here, we demonstrate for the first time that elevated CAD expression promotes CRC malignancy by enhancing proliferation, motility, and apoptosis resistance. Clinically, high CAD expression correlates with poor survival in CRC patients. Leveraging these findings, we developed a tumor microenvironment (TME)-responsive nickel‑copper nano‑heterojunction (NCSH@siCAD&AVT‑18A) that selectively releases hydrogen sulfide and copper ions in the acidic, reducing TME. This platform induces int

SUBMITTER: Xiang Y 

PROVIDER: S-EPMC12659243 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature