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Adv Healthc Mater. 2018 Jul;7(13):e1701366. doi: 10.1002/adhm.201701366. Epub 2018 Feb 13.

Broad-Spectrum Neutralization of Pore-Forming Toxins with Human Erythrocyte Membrane-Coated Nanosponges.

Author information

1
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA, 92093, USA.
2
The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
3
Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA.

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.

KEYWORDS:

antivirulence; bacterial infection; detoxification; hemolytic toxin; nanosponge

PMID:
29436150
PMCID:
PMC6041168
[Available on 2019-07-01]
DOI:
10.1002/adhm.201701366

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