Macrophage-mimicking nanodiscs for treating systemic infection caused by methicillin-resistant Staphylococcus aureus

Antibiotic-resistant bacteria represent a critical public health challenge, underscoring the urgent need for innovative therapeutic strategies. Inspired by the unique properties of cell membrane–derived nanodiscs, particularly their ultrasmall size and intrinsic membrane functions, we develop macrophage membrane–derived nanodiscs (denoted “MФ-NDs”) as a nanomedicine for the treatment of systemic bacterial infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Our findings demonstrate that MФ-NDs interact directly with bacteria, disrupting their membranes, inducing leakage of intracellular contents, and ultimately causing bacterial death. Meanwhile, MФ-NDs reduce intracellular bacterial count. In a mouse model of systemic MRSA infection, treatment with MФ-NDs significantly improves survival rates in both therapeutic and preventative contexts. Moreover, MФ-NDs show a lower propensity to induce bacterial resistance compared to conventional small-molecule antibiotics. No acute toxicity is observed in mice treated with MФ-NDs. Overall, this study underscores the straightforward fabrication and promising potential of MФ-NDs for addressing antibiotic-resistant bacterial infections.