The cytotoxic effects of glycyrrhizic acid-modified chitosan/selenium nanocomposite on osteosarcoma cancer cell line.

This study focuses on the preparation, characterization, and application of glycyrrhizic acid (GA)-modified chitosan/selenium (Cs/Se) nanocomposites (NC) for treating osteosarcoma cancer cells. The Cs-stabilized Se nanoparticles (Cs/Se NPs) were synthesized through a chemical reduction method, where GA was added via a surface modification technique to enhance biocompatibility and targeting efficiency. Characterization of the GA-Cs/Se NC and Cs/Se NPs was performed using various techniques, including transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Zeta potential analysis. These analyses confirmed the successful formation of spherical NPs with a uniform size (100–200 nm) and good distribution with appropriate surface modifications. GA-Cs/Se NC exhibited potent cytotoxicity against MG-63 osteosarcoma cells, with an IC50 of 76.65 ± 3.5 µg/ml, whereas it had negligible effects on bone marrow stromal cells, confirming selective tumor targeting. Additionally, gene expression analysis revealed an 8.07-fold upregulation of the pro-apoptotic Bax and a 0.36-fold downregulation of the anti-apoptotic Bcl-2, indicating mitochondrial-mediated apoptosis. Moreover, qRT-PCR revealed a 7.13-fold increase in p53 expression, corroborating the induction of DNA damage-induced apoptotic pathways. The novel GA-Cs/Se NC developed in this study uniquely integrates the ROS-mediated pro-apoptotic activity of Se NPs with the inhibitory and anti-inflammatory properties of GA, all within a Cs NPs matrix that improves stability, biocompatibility, and cellular uptake. This multifunctional design enables a synergistic mechanism combining oxidative stress induction with transcriptional modulation to selectively target and kill osteosarcoma cells while minimizing necrosis and inflammation.