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Broad-spectrum and powerful neutralization of bacterial toxins by erythroliposomes with the help of macrophage uptake and degradation

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Acta Pharmaceutica Sinica B 2022年第11期12卷 4235-4248页

作者： Chunying Liu Shuangrong Ruan Ying He Xuejing Li Yuefei Zhu Honglan Wang Hanwei Huang Zhiqing Pang School of Pharmacy Fudan UniversityKey Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 201203China The Institute for Biomedical Engineering&Nano Science Tongji University School of MedicineShanghai 200092China Department of Biomedical Engineering Columbia UniversityNew YorkNY 10027USA Institute of Hematology Union HospitalTongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430022China

Anti virulence strategy has been considered as one of the most promising approaches to combat drug-rcesistant bacterial infections.Porc-forming toxins(PFTs)are the largest class of bacterial toxins,inficting their virulence ffect through creating pores on the cell membrane.However,curent 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 biomimetic platform constructed by artificial lipid membranes and natural erythrocyle membranes,to necutralize different hemolytic PFTs regardless of their molecular structure.When tested with model PFTs,including a-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 eficiently neuralize various toxins and save animals'lives without causing damage to 0rgans 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-mediaed loxin degradation.

关键词： Eythroliposome Broad-spectrum detoxifcation Hybrid nanovesicle Pore-forming toxins Macrophage uptake Red blood cell membrane atificial lipid membrane

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