Mesenchymal Stem Cells Expressing CES1 and Soluble TRAIL Activate CPT-11 and Induce Apoptosis in Lung Cancer Brain Metastatic Lesions.

ABSTRACT: We aimed to develop a novel therapeutic strategy for lung cancer brain metastases by leveraging the tumor-tropic properties of genetically engineered Wharton's Jelly-derived mesenchymal stem cells (WJ-MSC) as vehicles for dual-agent gene therapy across the blood-brain barrier. WJ-MSCs were transiently engineered using lipid nanoparticle technology to coexpress soluble TRAIL (sTRAIL) and the prodrug-activating enzyme carboxylesterase 1 (CES1). In vitro analyses assessed transfection efficiency, therapeutic protein expression, apoptosis induction, and maintenance of stemness. Tumor-homing capacity was evaluated via EGFP labeling and intracerebral tracking. Therapeutic efficacy was tested in subcutaneous and intracerebral lung cancer xenograft models using bioluminescent imaging, histopatholo

SUBMITTER: Kim DO 

PROVIDER: S-EPMC12417980 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature