Broad-Spectrum Neutralization of Pore-Forming Toxins with Human Erythrocyte Membrane-Coated Nanosponges.
Broad-Spectrum Neutralization of Pore-Forming Toxins with Human Erythrocyte Membrane-Coated Nanosponges.
复制标题
DOI：
10.1002/adhm.201701366
复制
发表时间：
2018-07
影响因子：
10
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Chen Y;Chen M;Zhang Y;Lee JH;Escajadillo T;Gong H;Fang RH;Gao W;Nizet V;Zhang L
细菌毒素的中和已经成为治疗细菌感染的一种令人信服的方法，因为它可能对细菌耐药性的发展造成较少的选择性压力。目前，大多数毒素中和平台通过靶向毒素的分子结构起作用，这需要针对不同疾病进行毒素鉴定和定制设计。因此，它们的发展受到细菌毒素数量巨大和复杂性的挑战。在本文中，我们通过将人红细胞（hRBC）的膜涂覆到聚合物纳米颗粒上来配制仿生毒素纳米海绵，所述聚合物纳米颗粒作为毒素诱饵来吸收和中和广谱溶血毒素，而不管其分子结构如何。当用模型成孔毒素（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溶血素O和A组链球菌的溶血素O）测试时，hRBC纳米海绵能够以浓度依赖性方式完全抑制毒素诱导的溶血。此外，当对人脐静脉内皮细胞进行测试时，纳米海绵滞留的毒素没有显示出细胞毒性，并且当注射到小鼠中时没有显示出致死性，这共同表明有效的毒素中和。总体而言，结果证明了hRBC纳米海绵作为针对来自各种细菌菌株的溶血毒素的新型抗毒力平台的广泛适用性和高有效性。制备由人RBC膜制成的仿生毒素纳米海绵，并针对四种不同的成孔毒素进行测试。结果表明，纳米海绵可以在体外和体内以浓度依赖性方式完全抑制毒素的毒力。类似的设计和测试可以很容易地应用于其他细胞膜包被的纳米海绵，用于广泛的抗毒性应用。
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, we formulate biomimetic toxin nanosponges 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, the results demonstrate the broad applicability and high effectiveness of the hRBC nansoponges as a novel antivirulence platform against hemolytic toxins from various strains of bacteria. Biomimetic toxin nanosponges made of human RBC membranes are prepared and tested against four distinct pore-forming toxins. The results demonstrate that the nanosponges can completely inhibit the virulence of the toxins in a concentration-dependent manner both in vitro and in vivo. Similar design and test can be readily applied to other cell membrane-coated nanosponges for broad antivirulence applications.
登录
查看更多内容
DOI：
10.1083/jcb.200201081
发表时间：
2002-03-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Glomski IJ;Gedde MM;Tsang AW;Swanson JA;Portnoy DA
通讯作者：
Portnoy DA
一种吸收孔形成毒素的仿生纳米质体。
影响因子：
38.3
作者：
通讯作者：
--
影响因子：
5.4
作者：
Barczak, Amy K.;Hung, Deborah T.
通讯作者：
Hung, Deborah T.
影响因子：
38.3
作者：
通讯作者：
--
影响因子：
4.8
作者：
Timmer, Anjuli M.;Timmer, John C.;Nizet, Victor
通讯作者：
Nizet, Victor