Anti-virulence strategy has been considered as one of the most promising approaches to com-bat drug-resistant bacterial infections.Pore-forming toxins(PFTs)are the largest class of bacterial toxins,inflicting their virulence effect through creating pores on the cell membrane.However,current solutions for eliminating PFTs are mostly designed based on their molecular structure,requiring customized design for different interactions.In the present study,we employed erythroliposome(denoted as RM-PL),a bio-mimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes,to neutralize different hemolytic PFTs regardless of their molecular structure.When tested with model PFTs,including α-hemolysin,listeriolysin O,and streptolysin O,RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner.In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals'lives without causing damage to or-gans or tissues.In addition,we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes.In summary,the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mech-anism of lysosome-mediated toxin degradation.

Chunying Liu;Shuangrong Ruan;Ying He;Xuejing Li;Yuefei Zhu;Honglan Wang;Hanwei Huang;Zhiqing Pang

School of Pharmacy,Fudan University,Key Laboratory of Smart Drug Delivery,Ministry of Education,Shanghai 201203,China;The Institute for Biomedical Engineering&Nano Science,Tongji University School of Medicine,Shanghai 200092,China;Department of Biomedical Engineering,Columbia University,New York,NY 10027,USA;Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science&Technology,Wuhan 430022,China

药学学报（英文版）

[1]Chunying Liu;Shuangrong Ruan;Ying He;Xuejing Li;Yuefei Zhu;Honglan Wang;Hanwei Huang;Zhiqing Pang-.Broad-spectrum and powerful neutralization of bacterial toxins by erythroliposomes with the help of macrophage uptake and degradation)[J].药学学报（英文版）,2022(11):4235-4248

erythroliposomes,PFTs,inflicting,erythroliposome,listeriolysin,streptolysin

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