فهرست نشریات علمی دسترسی آزاد ایران

Cinnamaldehyde (CINAM), a natural compound with established anticancer properties, has limited clinical application due to its poor solubility and low bioavailability. Exosomes, which are cell-derived nanocarriers, offer a biocompatible platform for enhancing drug delivery and intracellular targeting. In this study, we evaluated the cytotoxic and molecular effects of CINAM-loaded mesenchymal stem cell–derived exosomes (EXO-CINAM) on colorectal cancer (Caco-2) cells. Exosomes were isolated and characterized using transmission electron microscopy (TEM), and CINAM loading was confirmed using high-performance liquid chromatography (HPLC). Cytotoxicity was assessed by sulforhodamine B (SRB) assay, apoptosis and cell cycle progression was analyzed by flow cytometry and DNA fragmentation assays, and ultrastructural changes were visualized by TEM. Western blotting and ELISA were employed to measure apoptotic protein expression, while qRT-PCR was used to examine gene expression related to apoptosis, inflammation, and angiogenesis. EXO-CINAM exhibited significantly greater cytotoxicity than free CINAM (IC₅₀: 23.87 µg/mL vs. 35.24 µg/mL, p < 0.01), with increased apoptosis (56.3% vs. 43.7%), G₀/G₁ apoptotic morphology confirmed by TEM, and DNA laddering indicating nuclear fragmentation. Protein analysis revealed elevated levels of cleaved caspase-3, -8, and -9, along with increased p53 and BAX levels and decreased BCL-2 levels. Gene expression analysis showed downregulation of NF-κB, MMP-2, MMP-9, and VEGFR2, and upregulation of CD95 and CD95L. IL-10 levels were also reduced, suggesting an anti-inflammatory effect of the treatment. Collectively, these findings indicate that exosomal delivery of CINAM enhances its anticancer activity by promoting apoptosis and suppressing inflammatory and angiogenic signaling, establishing EXO-CINAM as a promising nanotherapeutic platform for cancer treatment.