期刊
ADVANCED HEALTHCARE MATERIALS
卷 7, 期 13, 页码 -出版社
WILEY
DOI: 10.1002/adhm.201701366
关键词
antivirulence; bacterial infection; detoxification; hemolytic toxin; nanosponge
资金
- Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense [HDTRA1-14-1-0064]
- National Institutes of Health [R01EY025947]
- NATIONAL EYE INSTITUTE [R01EY025947] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007752] Funding Source: NIH RePORTER
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, -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.
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