Phytofabrication of Ag/CuO-Based Nanoantibiotics Functionalized with Amoxicillin Using Launaea resedifolia Extract: Synthesis, Characterization, and Biological Activities

Abstract

This study aims to develop and evaluate novel green-synthesized nanoantibiotics based on CuO/Ag nanocomposites functionalized with amoxicillin using Launaea resedifolia aqueous extract as a natural reducing, stabilizing, and capping agent. The work focuses on the eco-friendly fabrication of biocompatible nanomaterials with enhanced antimicrobial potential and investigates their physicochemical properties and multifunctional biological activities. The aqueous extract of L. resedifolia yielded 20% and was rich in bioactive phytochemicals, including flavonoids, tannins, saponins, alkaloids, and terpenoids. Quantitative analysis revealed total phenolic content (32.46 mg GAE/g), total flavonoid content (9.38 mg QE/g), and tannins (5.88 ± 0.7 mg CAE/g). LC–MS/MS analysis identified 22 phytoconstituents, dominated by L-proline (95.49%), along with other bioactive compounds such as berberine, oleanolic acid, catechin, quercetin derivatives, apigenin, resveratrol, and cinnamic acid, confirming strong antioxidant and therapeutic potential. The plant extract successfully mediated the green synthesis of CuO/Ag nanocomposites, as confirmed by XRD, UV–Vis spectroscopy, FTIR, SEM, and EDX analyses. The results indicated a crystalline CuO phase decorated with Ag nanoparticles, with an average crystallite size of 26.91 nm, and phytochemical capping derived from the extract. Successful loading of amoxicillin onto the nanocomposite was confirmed by FTIR spectral shifts and functional group interactions. Biological evaluations demonstrated that L. resedifolia extract exhibited notable antioxidant and moderate antibacterial activities, while CuO/Ag nanocomposites showed enhanced antibacterial and antibiofilm effects due to synergistic metal ion release, reactive oxygen species (ROS) generation, and membrane disruption mechanisms. Remarkably, the amoxicillin- functionalized CuO/Ag nanohybrids exhibited the highest performance across all assays, including antioxidant, anti-inflammatory, antibacterial, and antibiofilm activities against Escherichia coli, Klebsiella pneumoniae, and Bacillus subtilis, with biofilm inhibition reaching up to ~85% and significantly improved inhibition zones. Hemolytic analysis indicated acceptable biocompatibility of CuO/Ag nanocomposites, whereas amoxicillin-functionalized nanohybrids showed moderate hemolysis at higher concentrations due to enhanced membrane interactions. Overall, the findings demonstrate that Launaea resedifolia is an efficient green platform for the fabrication of multifunctional nanoantibiotics. The synergistic integration of plant phytochemicals, CuO/Ag nanostructures, and amoxicillin provides a promising therapeutic strategy for combating multidrug-resistant bacterial infections.