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Nanomedicine. 2019 Jul 23;21:102067. doi: 10.1016/j.nano.2019.102067. [Epub ahead of print]

Towards a nanoparticle-based prophylactic for maternal autoantibody-related autism.

Author information

1
University of California, Davis, Department of Biomedical Engineering, Davis, CA, USA.
2
University of California, Davis, Peter A. Rock Thermochemistry Laboratory and NEAT, Davis, CA, USA.
3
University of California, Davis, Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, Davis, CA, USA.
4
University of California, Davis, Department of Pathology Microbiology and Immunology, Davis, CA, USA.
5
University of California, Davis, Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, Davis, CA, USA; University of California, Davis, M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders), Davis, CA, USA.
6
University of California, Davis, Department of Biomedical Engineering, Davis, CA, USA. Electronic address: jamlewis@ucdavis.edu.

Abstract

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/cm2). 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.

KEYWORDS:

Iron oxide(2); Maternal autoantibody-related autism(1); Peptide-functionalized(4); nanoparticles(3)

PMID:
31349087
DOI:
10.1016/j.nano.2019.102067

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