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.
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。
