迈向基于纳米颗粒的母体自身抗体相关性自闭症预防策略。
Towards a nanoparticle-based prophylactic for maternal autoantibody-related autism.
机构信息
University of California, Davis, Department of Biomedical Engineering, Davis, CA, USA.
University of California, Davis, Peter A. Rock Thermochemistry Laboratory and NEAT, Davis, CA, USA.
出版信息
Nanomedicine. 2019 Oct;21:102067. doi: 10.1016/j.nano.2019.102067. Epub 2019 Jul 23.
Recently, the causative agents of Maternal Autoantibody-Related (MAR) autism, pathological autoantibodies and their epitopic targets (e.g. lactate dehydrogenase B [LDH B] peptide), have been identified. Herein, we report on the development of Systems for Nanoparticle-based Autoantibody Reception and Entrapment (SNAREs), which we hypothesized could scavenge disease-propagating MAR autoantibodies from the maternal blood. To demonstrate this functionality, we synthesized 15 nm dextran iron oxide nanoparticles surface-modified with citric acid, methoxy PEG(10 kDa) amine, and LDH B peptide (33.8 μg peptide/cm). In vitro, we demonstrated significantly lower macrophage uptake for SNAREs compared to control NPs. The hallmark result of this study was the efficacy of the SNAREs to remove 90% of LDH B autoantibody from patient-derived serum. Further, in vitro cytotoxicity testing and a maximal tolerated dose study in mice demonstrated the safety of the SNARE formulation. This work establishes the feasibility of SNAREs as the first-ever prophylactic against MAR autism.
最近，已经确定了与母体自身抗体相关（MAR）自闭症的病原体、病理性自身抗体及其表位靶点（例如乳酸脱氢酶 B [LDH B] 肽）。在此，我们报告了基于纳米粒子的自身抗体接收和捕获系统（SNAREs）的开发，我们假设这些系统可以从母体血液中清除传播疾病的 MAR 自身抗体。为了证明这一功能，我们合成了表面经过柠檬酸、甲氧基聚乙二醇（10 kDa）胺和 LDH B 肽（33.8μg 肽/cm）修饰的 15nm 葡聚糖氧化铁纳米粒子。体外实验结果表明，与对照纳米粒子相比，SNAREs 被巨噬细胞摄取的程度显著降低。这项研究的标志性结果是 SNAREs 能够从患者来源的血清中去除 90%的 LDH B 自身抗体。此外，体外细胞毒性试验和小鼠最大耐受剂量研究表明 SNARE 制剂具有安全性。这项工作确立了 SNAREs 作为预防 MAR 自闭症的首个可行方案。
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