CELL INTELLIGENCE · 肿瘤细胞治疗研究

Glioblastoma multiforme (GBM) remains a highly aggressive brain tumor with limited therapeutic options. MicroRNA-10b (miR-10b) is consistently overexpressed in GBM and absent in normal astrocytes, making it a potential therapeutic target. In this study, we evaluated the feasibility of using human umbilical cord mesenchymal stem cell (hUC-MSC)-derived exosomes as delivery vehicles for Locked Nucleic Acid anti-miR-10b-5p (LNA-anti-10b) in U87MG glioblastoma cells. Exosomes were isolated by ultracentrifugation and loaded with LNA-anti-10b. Delivery efficiency was compared with lipofectamine-mediated transfection. The functional effects of exosome-loaded anti-10b (E-LNA-anti-10b) were assessed in both 2D and 3D culture systems. Cell viability and apoptosis were evaluated using Annexin V/PI, AO/PI, and MTT assays, while migration assays assessed cellular aggressiveness. The expression of validated miR-10b target genes and epithelial-mesenchymal transition (EMT)-related markers was analyzed by quantitative RT-PCR and Western blotting. hUC-MSC-derived exosomes efficiently delivered LNA-anti-10b to U87MG cells in both 2D and 3D culture models. E-LNA-anti-10b treatment was associated with enhanced reductions in cell viability, proliferation, migration, and expression of EMT-associated markers. Notably, na ve hUC-MSC-derived exosomes also exhibited intrinsic anti-proliferative and anti-migratory effects. Together, these findings indicate that hUC-MSC-derived exosomes possess inherent anti-tumor properties in GBM models and can functionally enhance the effects of LNA-anti-10b delivery.