Quaternary Ammonium-Cu ₂ O Nanocomposite with Synergistic Multimode Antibacterial Action for Eradicating MRSA and Mitigating Resistance Development

The overuse of antibiotics has accelerated the emergence of multidrug-resistant bacterial strains, often leading to the failure of conventional antibiotic therapies. However, the development of different classes of antibiotics has lagged significantly behind the spread of bacterial multidrug resistance. Therefore, there is an urgent need to develop alternative antibacterial agents or therapeutic strategies that employ diverse antimicrobial mechanisms and exhibit a low propensity for inducing bacterial resistance. In this study, a poly(diallyl dimethyl ammonium chloride) (PDDA)-Cu2O nanocomposite was synthesized and evaluated for its efficacy against methicillin-resistant Staphylococcus aureus (MRSA). This nanocomposite combines the bacterial membrane-targeting ability of PDDA with the intrinsic antibacterial activity of Cu2O. Furthermore, the near-infrared (NIR) photothermal effect and peroxidase-like activity of Cu2O synergistically enhanced the composite’s antibacterial performance. Within a short irradiation time (10 min), PDDA-Cu2O + H2O2 achieved a 3.7 log10 reduction of MRSA, surpassing the results obtained with PDDA-Cu2O alone (1.6 log10), PDDA-Cu2O + NIR (2.3 log10), and PDDA-Cu2O + H2O2 without irradiation (2.5 log10). Moreover, PDDA-Cu2O demonstrated a low tendency to induce bacterial resistance and low cytotoxicity toward mouse astrocyte C8-D1A cells. Collectively, this multiple-mode antibacterial platform based on PDDA-Cu2O may offer a promising strategy to combat refractory MRSA infections.