Chen Haitao, Kaminski Michael D, Liu Xianqiao, Mertz Carol J, Xie Yumei, Torno Michael D, Rosengart Axel J
Neurocritical Care and Acute Stroke Program, Department of Neurology, The University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue, MC 2030, Chicago, IL 60637, USA.
Med Hypotheses. 2007;68(5):1071-9. doi: 10.1016/j.mehy.2005.04.047. Epub 2006 Nov 22.
We describe the conceptual approach, theoretical background and preliminary experimental data of a proposed platform technology for specific and rapid decorporation of blood-borne toxins from humans. The technology is designed for future emergent in-field or in-hospital detoxification of large numbers of biohazard-exposed victims; for example, after radiological attacks. The proposed systems is based on nanoscale technology employing biocompatible, superparamagnetic nanospheres, which are functionalized with target-specific antitoxin receptors, and freely circulate within the human blood stream after simple intravenous injection. Sequestration of the blood-borne toxins onto the nanosphere receptors generates circulating nanosphere-toxin complexes within a short time interval; mathematical modeling indicates prevailing of unbound nanosphere receptors over target toxin concentrations at most therapeutic injection dosages. After a toxin-specific time interval nanosphere-toxin complexes are generated within the blood stream and, after simple arterial or venous access, the blood is subsequently circulated via a small catheter through a portable high gradient magnetic separator device. In this device, the magnetic toxin complexes are retained by a high gradient magnetic field and the detoxified blood is then returned back to the blood circulation (extracorporeal circulation). Our preliminary in vitro experiments demonstrate >95% first pass capture efficiency of magnetic spheres within a prototype high gradient magnetic separation device. Further, based on the synthesis of novel hydrophobic magnetite nanophases with high magnetization ( approximately 55 emu/g), the first biodegradable magnetic nanospheres at a size range of approximately 280 nm and functionalized with PEG-maleimide surface groups for specific antibody attachment are described here. In future applications, we envision this technology to be suitable for emergent, in-field usage for acutely biohazard exposed victims as both the injectable toxin-binding magnetic spheres and the separator device are made to be portable, light-weight, zero-power, and self- or helper-employed. Details of the technology are presented and the state-of-knowledge and research is discussed.
我们描述了一种用于从人体血液中特异性快速去除血源毒素的拟议平台技术的概念方法、理论背景和初步实验数据。该技术旨在未来对大量暴露于生物危害的受害者进行现场或医院紧急解毒；例如，在放射性攻击之后。拟议的系统基于纳米技术，采用生物相容性超顺磁性纳米球，这些纳米球用靶向特异性抗毒素受体进行功能化，在简单静脉注射后可在人体血流中自由循环。血源毒素与纳米球受体结合，在短时间内形成循环的纳米球 - 毒素复合物；数学模型表明，在大多数治疗注射剂量下，未结合的纳米球受体数量超过目标毒素浓度。在特定的毒素作用时间间隔后，纳米球 - 毒素复合物在血流中形成，然后在简单的动脉或静脉接入后，血液通过一根小导管经便携式高梯度磁分离装置进行循环。在该装置中，磁性毒素复合物被高梯度磁场捕获，解毒后的血液随后返回血液循环（体外循环）。我们初步的体外实验表明，在原型高梯度磁分离装置中，磁球的首过捕获效率大于95%。此外，基于合成具有高磁化强度（约55 emu/g）的新型疏水性磁铁矿纳米相，本文描述了首批尺寸范围约为280 nm、用聚乙二醇 - 马来酰亚胺表面基团功能化以用于特异性抗体附着的可生物降解磁性纳米球。在未来的应用中，我们设想该技术适用于对急性暴露于生物危害的受害者进行现场紧急使用，因为可注射的毒素结合磁球和分离装置都设计为便携式、轻量级、零功耗且可自行或辅助使用。本文介绍了该技术的细节，并讨论了相关知识和研究现状。
