Broad‐Spectrum Neutralization of Pore‐Forming Toxins with Human Erythrocyte Membrane‐Coated Nanosponges,Advanced Healthcare Materials

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Broad‐Spectrum Neutralization of Pore‐Forming Toxins with Human Erythrocyte Membrane‐Coated Nanosponges
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2018-02-13 , DOI: 10.1002/adhm.201701366
Yijie Chen _{1,

2} , Mengchun Chen _{1,

2} , Yue Zhang ₁ , Joo Hee Lee ₁ , Tamara Escajadillo ₃ , Hua Gong ₁ , Ronnie H Fang ₁ , Weiwei Gao ₁ , Victor Nizet ₃ , Liangfang Zhang ₁

Affiliation

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：

用人红细胞膜涂层纳米海绵广谱中和成孔毒素

细菌毒素的中和已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造成较小的选择性压力。目前，大多数毒素中和平台都是针对毒素的分子结构发挥作用，这需要针对不同的疾病进行毒素识别和定制设计。因此，它们的发展受到细菌毒素数量巨大和复杂性的挑战。在此，仿生毒素纳米海绵是通过将人红细胞（hRBC）膜涂覆在聚合物纳米粒子上而配制而成，该聚合物纳米粒子充当毒素诱饵，吸收和中和广谱溶血毒素，无论其分子结构如何。当使用模型成孔毒素（包括蜂毒肽、耐甲氧西林金黄色葡萄球菌的 α-溶血素、单核细胞增生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）进行测试时，hRBC 纳米海绵能够完全抑制毒素诱导的溶血。浓度依赖性方式。此外，纳米海绵滞留的毒素在人脐静脉内皮细胞上测试时没有显示出细胞毒性，并且在注射到小鼠体内时也没有显示出致死性，这共同表明了有效的毒素中和作用。总体而言，这些结果证明了 hRBC 纳米海绵作为针对各种细菌菌株溶血毒素的新型抗毒力平台具有广泛的适用性和高效性。

更新日期：2018-02-13

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