Next-generation nanoformulation: Glycyrrhiza glabra-based chitosan-curcumin MgO/Fe2O3 nanocomposite for targeted lung cancer therapy with dual antioxidant action.

This study aims to develop and evaluate Glycyrrhiza glabra-based magnesium oxide/iron oxide nanocomposite (NC) functionalized with chitosan and curcumin to enhance therapeutic efficacy against lung cancer and oxidative stress. This is the first report integrating G. glabra extract with chitosan and curcumin functionalization into a MgO/Fe₂O₃ nanocomposite for enhanced antioxidant and anticancer effects. The developed nanocomposite demonstrated strong biocompatibility and in vitro therapeutic efficacy, as evidenced by low cytotoxicity in normal cells and significant inhibitory effects against A549 lung cancer cells. In this study, bioactive phytochemical-loaded G. glabra extract was used as a green capping and reducing agent to synthesize MgO/Fe₂O₃ NC. The nanomaterials were also functionalized with curcumin and chitosan to promote stability, bioavailability, and site-specific pharmacological activity. The synthesis process was carried out under green conditions, in which the nanocomposite was characterized using FTIR, UV-Vis spectroscopy, EDX analysis, zeta potential analysis, HR-TEM, and XRD. The antioxidant potential was assessed through the DPPH free radical scavenging activity, whereby MgO/Fe₂O₃-chitosan-curcumin NCs yielded the maximum inhibition of free radicals (IC₅₀ = 0.0977 mg/mL) when compared to other nanomaterials. Antimicrobial activity was assessed against Gram-negative and Gram-positive bacteria, wherein MgO/Fe₂O₃ NC showed moderate activity, and chitosan and curcumin functionalization reduced this to some extent by possibly controlled release behavior or protection of active sites. Cytotoxicity against A549 human lung cancer cells showed strong inhibition by the MgO/Fe₂O₃-chitosan-curcumin NC (IC₅₀ = 10 µg/mL), confirmed by changes in morphology in accordance with apoptosis. In addition, in silico ADME simulation suggested favorable bioavailability and low toxicity, which is an indicator of the therapeutic potential of these NCs. To the best of our knowledge, this is the first report on G. glabra-mediated green synthesis with dual functionalization of chitosan and curcumin in a MgO/Fe₂O₃ nanocomposite. The formulation has synergistic antioxidant and anticancer activity with vast potential in lung cancer therapy. As a whole, the findings address the dual antioxidant and anticancer properties of G. glabra-derived MgO/Fe₂O₃-chitosan-curcumin NC and their green potential as agents in the treatment of lung cancer. In vivo studies are recommended to confirm efficacy and safety.