Engineering Copper Oxide–DNA nanocomposites as Novel Antibacterial Nanomaterials Against Antimicrobial Resistance

Abstract

The rapid emergence of antimicrobial resistance (AMR) has become a major global health concern, reducing the effectiveness of conventional antibiotics and increasing the demand for alternative antimicrobial strategies. The aim of this work is try to overcome the problem of antibiotic resistance by developing a nano-product used as a selective antimicrobial agent. In this study, copper oxide nanoparticles (CuO NPs) were synthesized using a chemical reduction–precipitation method with ascorbic acid as a reducing agent. Furthermore, CuO-based nanocomposites functionalized with bacterial DNA extracted from Escherichia coli and Staphylococcus aureus were developed to investigate their potential as selective antibacterial agents. The synthesized Nano-composites were characterized using UV–Visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). UV–Vis analysis confirmed nanoparticle formation through characteristic absorption peaks, while FTIR spectra revealed the presence of Cu–O bonds and functional groups associated with bacterial DNA conjugation. XRD analysis confirmed the successful formation of crystalline Cu₂O structures, with crystallite sizes ranging from approximately 8.1 to 11.8 nm. SEM observations revealed aggregated nanoscale structures with heterogeneous morphologies, further confirming the formation of CuO–DNA nanocomposites. The biological activities of the synthesized nanoparticles were evaluated through antioxidant, anti-inflammatory, and antibacterial assays. CuO npsexhibited strong antioxidant activity, showing the lowest IC₅₀ value (1.13 µg/mL), whereas Staphylococcus aureus-nanoparticles (S-CuNPs) demonstrated the highest anti-inflammatory activity, with an IC₅₀ value of 0.5 µg/mL. Antibacterial activity, assessed using the disk diffusion method, revealed that DNA-functionalized nanoparticles exhibited enhanced antibacterial effects compared with CuO npsalone. The highest inhibition zone was observed for E-CuNPs against Escherichia coli at 40 mg/mL, while S-CuNPs showed superior activity against Staphylococcus aureus, suggesting possible strain-specific interactions between the nanocomposites and their corresponding bacterial targets. In addition, molecular docking studies demonstrated favorable interactions between Cu₂O nanoparticles and bacterial DNA gyrase-related proteins. The strongest binding affinity was observed for receptor 8BN6 (−4.82 kcal/mol), supporting the proposed antibacterial mechanism through interference with bacterial DNA replication processes. Overall, these findings indicate that DNA-functionalized copper oxide nanoparticles represent a promising and innovative strategy for to developing selective and efficient antibacterial nanomaterials capable of combating antibiotic-resistant bacteria.