TY - JOUR
T1 - Towards a nanoparticle-based prophylactic for maternal autoantibody-related autism
AU - Bolandparvaz, Amir
AU - Harriman, Rian
AU - Alvarez, Kenneth
AU - Lilova, Kristina
AU - Zang, Zexi
AU - Lam, Andy
AU - Edmiston, Elizabeth
AU - Navrotsky, Alexandra
AU - Vapniarsky, Natalia
AU - Van De Water, Judy
AU - Lewis, Jamal S.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - Iron oxide
KW - Maternal autoantibody-related autism
KW - Peptide-functionalized
KW - nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85070590101&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070590101&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2019.102067
DO - 10.1016/j.nano.2019.102067
M3 - Article
C2 - 31349087
AN - SCOPUS:85070590101
SN - 1549-9634
VL - 21
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
M1 - 102067
ER -