Macrophage-mimicking nanodiscs for treating systemic infection caused by methicillin-resistant <i>Staphylococcus aureus</i>.

Abstract

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 <i>Staphylococcus aureus</i> (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.