Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
Colloids Surf B Biointerfaces. 2019 Feb 1;174:95-102. doi: 10.1016/j.colsurfb.2018.11.002. Epub 2018 Nov 3.
Systemic inflammation such as sepsis represents an acute life-threatening condition, to which often no timely remedy can be found. A promising strategy may be to functionalize magnetic nanoparticles with specific peptides, derived from the binding motives of agglutinating salivary proteins, that allow immobilization of pathogens. In this work, superparamagnetic iron oxide nanoparticles with stable polycondensed aminoalkylsilane layer were developed, to which the heterobifunctional linkers N-succinimidyl 3-(2-pyridyldithio)-propanoate (SDPD) and N-succinimidyl bromoacetate (SBA) were bound. These linkers were further chemoselectively reacted with the thiol group of singularly present cysteines of selected peptides. The resulting functional nanoparticles underwent a detailed physicochemical characterization. The biocompatibility of the primarily coated aminoalkylsilane particles was also investigated. To test the pathogen-binding efficacy of the particles, the lipopolysaccharide-immobilization capacity of the peptide-coated particles was compared with free peptides. Here, one particle-bound peptide species succeeded in capturing 90% of the toxin, whereas the degree of immobilization of the toxin with a system that varied in the sequence of the peptide dropped to 35%. With these promising results, we hope to develop extracorporeal magnetic clearance systems for removing pathogens from the human body in order to accelerate diagnosis and alleviate acute disease conditions such as sepsis.
全身性炎症（如败血症）代表了一种急性的、危及生命的病症，往往无法及时找到有效的治疗方法。一种有前途的策略可能是通过特定的肽将磁性纳米粒子功能化，这些肽来源于凝集唾液蛋白的结合基序，可以固定病原体。在这项工作中，开发了具有稳定聚缩氨基烷基硅烷层的超顺磁性氧化铁纳米粒子，将异双功能连接剂 N-琥珀酰亚胺基 3-(2-吡啶基二硫代）-丙酸酯（SDPD）和 N-琥珀酰亚胺基溴乙酸酯（SBA）连接到这些连接剂上。这些连接剂进一步与选定肽中单个存在的半胱氨酸的巯基进行化学选择性反应。所得功能化纳米粒子经历了详细的物理化学特性分析。还研究了初步涂覆的氨基烷基硅烷颗粒的生物相容性。为了测试颗粒的病原体结合效果，将肽涂覆的颗粒的脂多糖固定能力与游离肽进行了比较。在这里，一种颗粒结合的肽物种成功捕获了 90%的毒素，而毒素与肽序列不同的系统的固定程度下降到 35%。有了这些有希望的结果，我们希望开发体外磁清除系统，从人体中去除病原体，以加速诊断并缓解败血症等急性疾病状况。
