一种以Fe3O4@SiO2为核壳的磁性纳米材料作为新型血液灌流吸附剂治疗重金属中毒的可行性研究

China is one of the most heavily polluted countries by heavy metals, seriously endangering national health.. At present, the treatment of heavy metal poisoning to chelating agent-based, but there is a long treatment cycle, treatment is not complete, kidney toxicity and other defects. Hemoperfusion is an effective treatment for heavy metal poisoning. However, the existing perfusants have poor selectivity, low removal rate of heavy metals, and high dependence on imports and high cost. Therefore, the research and development of new perfusers with high efficiency, high selectivity and high biosecurity is imminent.. In this study, a magnetic nanoparticle modified with Fe3O4 @ SiO2 as the core-shell and different functional compounds was prepared. While obtaining high efficient adsorption rates of heavy metals, the blood compatibility was investigated by hemolysis, coagulation, platelet aggregation and so on. The histocompatibility was detected by cytotoxicity, bacterial adhesion and immunotoxicity.. Establishment of large animal heavy metal poisoning model, connecting the blood circulation pathway in vitro. The biodegradable materials were selected as the new perfusants to study the adsorption and possible mechanism of heavy metals in the body. At the same time, we evaluated the in vivo toxicity caused by the contact between the material and the blood from the aspects of blood iochemistry, organ toxicity and homeostasis.

我国是世界上重金属污染最严重、最广泛的国家之一，重金属污染严重危害国民健康。. 目前治疗以药物螯合剂为主，但存在治疗周期长、治疗不彻底、肾脏毒副作用大等弊端。血液灌流是重金属中毒的有效治疗方法，然而现有灌流剂选择性差，清除率低，多依赖进口且成本高，因此高效、高选择性、高生物安全性的新型灌流剂研发迫在眉睫。. 本研究拟合成一种以Fe3O4@SiO2为核壳，不同功能化合物表面修饰的磁性纳米颗粒。在获得高效重金属吸附率的同时，通过溶血，凝血，血小板凝集实验等考察血液相容性，通过细胞毒性，细菌粘附，免疫毒性等检测组织相容性。. 建立大动物重金属中毒模型，将筛选出的生物相容性好的纳米材料作为血液灌流剂，研究其对体内重金属的吸附及可能机制；同时，从血生化，脏器毒性，内环境稳态等多方面评价材料与血液接触时引起的体内毒性，积累基础医学数据，为临床有效，可行的新型灌流剂研发提供理论依据。

我国是世界上重金属污染最广泛，最严重的国家之一；严重危害国民健康。目前尚无特异性治疗手段，临床仍以药物螯合剂为主。但存在治疗周期长，不彻底，肝肾毒性大等弊端。铅在机体血液-组织-器官间处于动态平衡，血液灌流是铅中毒的有效治疗方法。然而现有灌流剂选择性差、清除率低且成本高昂；高效、高选择性、高生物安全性的灌流剂及配套装置研发迫在眉睫。. 本研究拟合成一种以Fe3O4为核心，不同功能化合物修饰的磁性纳米颗粒。在获得高效重金属铅、镉吸附率的同时，通过溶血，抗凝血等考察血液相容性；通过细胞毒性，免疫炎症反应等检测组织相容性，筛选出生物相容性好的纳米颗粒作为血液灌流剂，并设计基于“微流控-磁铁分离技术”的配套灌流装置。在大动物铅中毒模型中进行活体灌流，研究血铅清除效率及可能机制。并从脏器毒性、内环境稳态、炎症反应等多方面进行安全性评价，均获得了良好的研究结果。为临床铅中毒新疗法研发积累基础数据，有望填补国内透析材料领域的技术空白，有巨大的临床应用前景。