Differential Modulation of Biofilm-associated Gene Expression by Ag and ZnO Quantum Dots in Gram-positive and Gram-negative Bacteria: Implications for Cutaneous Wound Healing

The rise of multidrug-resistant (MDR) pathogens, particularly biofilm-forming bacteria such as Acinetobacter baumannii and Staphylococcus aureus, poses a severe threat to global health. Biofilms significantly increase antibiotic resistance and complicate wound infections. This study aimed to synthesize silver quantum dots (Ag-QDs) and zinc oxide quantum dots (ZnO-QDs) using a green hydrothermal method and evaluate their comparative antibacterial, anti-biofilm, and wound-healing efficacy. QDs were synthesized via a hydrothermal method using oak fruit extract as a reducing and stabilizing agent. The nanoparticles were characterized using UV/vis spectroscopy and transmission electron microscopy. The minimum inhibitory concentration (MIC) against clinical and standard strains of A. baumannii and S. aureus was determined. Anti-biofilm activity was assessed using the microtiter plate assay. The effect of sub-MIC concentrations on the expression of key biofilm-related genes (bap and ompA in A. baumannii; icaA and icaD in S. aureus) was evaluated using Real-time PCR. An in vivo study was conducted on Balb/c mice with infected excisional wounds to evaluate wound healing and bacterial load reduction over 14 days. The synthesized QDs were spherical with an average size of less than 10 nm. Ag-QDs exhibited a lower MIC (average: 125 µg/mL) compared to ZnO-QDs (average: 275 µg/mL) against both bacteria. Both QDs significantly inhibited biofilm formation (p<0.05). Gene expression analysis revealed that Ag QDs caused a more pronounced downregulation of biofilm genes (2.5 to 5-fold reduction) compared to ZnO-QDs (1.5 to 3-fold reduction). In the mouse model, wounds treated with Ag-QDs showed superior healing rates, reduced inflammation, and a more significant decrease in bacterial load compared to ZnO-QDs and the antibiotic control group. Biosynthesized Ag-QDs and ZnO-QDs demonstrate significant anti-biofilm and wound-healing properties. Ag-QDs showed greater potency in inhibiting biofilm gene expression and promoting wound healing in S. aureus and A. baumannii infections. These findings suggest that quantum dots, particularly Ag-QDs, are promising nanotherapeutic agents against biofilm-associated wound infections caused by MDR bacteria.