Broad‐Spectrum Neutralization of Pore‐Forming Toxins with Human Erythrocyte Membrane‐Coated Nanosponges
Abstract
Neutralization of bacterial toxins has become a compelling approach to treating bacterial infections as it may pose less selective pressure for the development of bacterial resistance. Currently, the majority of toxin neutralization platforms act by targeting the molecular structure of the toxin, which requires toxin identification and customized design for different diseases. Therefore, their development has been challenged by the enormous number and complexity of bacterial toxins. Herein, biomimetic toxin nanosponges are formulated by coating membranes of human red blood cells (hRBCs) onto polymeric nanoparticles, which act as a toxin decoy to absorb and neutralize a broad‐spectrum of hemolytic toxins regardless of their molecular structure. When tested with model pore‐forming toxins, including melittin, α‐hemolysin of methicillin‐resistant Staphylococcus aureus, listeriolysin O of Listeria monocytogenes, and streptolysin O of Group A Streptococcus, the hRBC nanosponges are able to completely inhibit toxin‐induced hemolysis in a concentration‐dependent manner. In addition, the nanosponge‐detained toxins show no cytotoxicity when tested on human umbilical vein endothelial cells and no lethality when injected into mice, which together indicate effective toxin neutralization. Overall, these results demonstrate the broad applicability and high effectiveness of the hRBC nanosponges as a novel antivirulence platform against hemolytic toxins from various strains of bacteria.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 13, 2018
- Source ID
- 10.1002/adhm.201701366
Entities
People
- Hua Gong
- Joo Hee Lee
- Liangfang Zhang
- Mengchun Chen
- Ronnie H Fang
- Tamara Escajadillo
- Victor Nizet
- Weiwei Gao
- Yijie Chen
- Yue Zhang
Organizations
- Defense Threat Reduction Agency
- National Institutes of Health
- University of California, San Diego
- Wenzhou Medical University