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.

中文翻译：

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人体红细胞膜包被的纳米海绵对形成孔毒素的广谱中和

细菌毒素的中和已经成为治疗细菌感染的一种引人注目的方法，因为它可能对细菌耐药性的发展产生较小的选择压力。当前，大多数毒素中和平台通过靶向毒素的分子结构起作用，这需要毒素鉴定和针对不同疾病的定制设计。因此，它们的发展受到细菌毒素数量巨大和复杂性的挑战。在这里，仿生毒素纳米海绵是通过将人类红细胞（hRBC）的膜涂在聚合物纳米颗粒上而制成的，该纳米颗粒充当毒素诱饵，吸收和中和各种溶血毒素，无论其分子结构如何。用模型造孔毒素（包括蜂毒肽，耐甲氧西林的α-溶血素）进行测试时金黄色葡萄球菌，单核细胞增生性李斯特菌的李斯特菌溶血素O和A组链球菌的链球菌溶血素O ，hRBC纳米海绵能够以浓度依赖的方式完全抑制毒素诱导的溶血。此外，用纳米海绵保留的毒素在人脐静脉内皮细胞上进行测试时没有细胞毒性，注射到小鼠中也没有致死性，这表明毒素被有效地中和了。总体而言，这些结果表明，hRBC纳米海绵作为新型抗病毒平台，可抵抗各种细菌的溶血毒素，具有广泛的适用性和高效性。