Broad-spectrum and powerful neutralization of bacterial toxins by erythroliposomes with the help of macrophage uptake and degradation.
10.1016/j.apsb.2022.03.015
- Author:
Chunying LIU
1
;
Shuangrong RUAN
2
;
Ying HE
1
;
Xuejing LI
1
;
Yuefei ZHU
1
;
Honglan WANG
3
;
Hanwei HUANG
1
;
Zhiqing PANG
1
Author Information
1. School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China.
2. The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, China.
3. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430022, China.
- Publication Type:Journal Article
- Keywords:
Artificial lipid membrane;
Broad-spectrum detoxification;
Erythroliposome;
Hybrid nanovesicle;
Macrophage uptake;
Pore-forming toxins;
Red blood cell membrane
- From:
Acta Pharmaceutica Sinica B
2022;12(11):4235-4248
- CountryChina
- Language:English
-
Abstract:
Anti-virulence strategy has been considered as one of the most promising approaches to combat 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 biomimetic 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 organs 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 mechanism of lysosome-mediated toxin degradation.
