Decoy Extracellular Vesicles Overcome Triple-Negative Breast Cancer Heterogeneity via Membrane-Cytoplasm-Mitochondria Cascade Targeting.

ABSTRACT: Triple-negative breast cancer (TNBC) exhibits multilevel heterogeneity, including differences in stemness, immune checkpoint (IC) upregulation, and metabolic plasticity, which has resulted in a lack, of comprehensive treatment strategies. Extracellular vesicles (EVs) from exhausted T cells contain high levels of ICs, which allow them to target and block multiple IC ligands in tumor cells, including cancer stem cells (CSCs). TEAD4 is identified as a pivotal gene facilitating CSC growth and immune escape. Consequently, a novel EV delivery system (siT/MOF@EVs), which targets the tumor cell membrane-cytoplasm-mitochondria cascade, is engineered to codeliver TEAD4-siRNA (siTEAD4) and a mitochondria-targeting metal-organic framework (T/MOF) to overcome tumor heterogeneity. Extracellularly, EVs a

SUBMITTER: Chen C 

PROVIDER: S-EPMC12561465 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature