Synthesis of Erythrocyte Nanodiscs for Bacterial Toxin Neutralization

Nanodiscs are a compelling nanomedicine platform due to their ultrasmall size and distinct disc shape. Current nanodisc formulations are made primarily with synthetic lipid bilayers and proteins. Here, we report a cellular nanodisc made with human red blood cell (RBC) membrane (denoted "RBC-ND") and show its effective neutralization against bacterial toxins. In vitro, RBC-ND neutralizes the hemolytic activity and cytotoxicity caused by purified α-toxin or complex whole secreted proteins (wSP) from methicillin-resistant Staphylococcus aureus bacteria. In vivo, RBC-ND confers significant survival benefits for mice intoxicated with α-toxin or wSP in both therapeutic and prevention regimens. Moreover, RBC-ND shows good biocompatibility and biosafety in vivo. Overall, RBC-ND distinguishes itself by inheriting the biological functions of the source cell membrane for bioactivity. The design strategy of RBC-ND can be generalized to other types of cell membranes for broad applications.