Novel Cu4MgO5 nanoparticles: Investigating anticancer, antibacterial, anti-biofilm, and fimH gene-related biofilm inhibition in Uropathogenic Escherichia coli

Abstract

Uropathogenic Escherichia coli is the primary cause of urinary tract infections (UTIs). The fimH gene, which encodes an adhesin on type 1 pili, facilitates UPEC colonization and biofilm formation. Due to the high prevalence of UPEC-associated urinary tract infections and the increasing antibiotic resistance related to UPEC, the need for new therapeutic strategies is crucial. This study aimed to design and synthesize novel Cu₄MgO₅ nanoparticles, investigate anticancer activity, antibacterial and antibiofilm effects, and inhibition of the fimH gene on UPEC. In this study, Cu₄MgO₅ nanoparticles were synthesized via sol-gel auto-combustion method, and their properties were characterized using XRD, FT-IR, EDX, SEM, TEM, and zeta potential analyses. Characterization showed a pure Cu₄MgO₅ phase at 700 °C with spherical-like morphology (average size: 172.84 nm) and a zeta potential of −14.9 mV, indicating moderate colloidal stability. Based on results, the nanoparticles showed anticancer activity against HTB-5 bladder cancer cells (IC₅₀ = 96.33 μg/mL at 24 h; 32.41 μg/mL at 48 h), and low toxicity to HDF normal cells (IC₅₀ = 1039 μg/mL at 24 h; 624 μg/mL at 48 h). Antibacterial activity of the nanoparticles was assessed by minimum inhibitory concentration (MIC) test and the broth microdilution method. Based on the results, the MIC values of nanoparticles were 7.81–31.25 μg/mL against fifteen clinical isolates of UPEC that were recovered from hospitalized UTI patients and the standard E. coli ATCC 25922 isolate. At sub-MIC concentrations, Cu₄MgO₅ nanoparticles reduced UPEC biofilm formation by an average of 53 % and downregulated expression of biofilm-associated fimH gene by an average of 72.9 % (a 3.68-fold reduction) in both clinical and standard isolates. These findings demonstrate the potential of novel Cu₄MgO₅ nanoparticles as a promising therapeutic approach for managing UPEC-associated UTIs by targeting bacterial growth and biofilm formation. However, further in vitro and in vivo studies are necessary.