Biodistribution and toxicity of epitope‐functionalized dextran iron oxide nanoparticles in a pregnant murine model

Autor: Amir Bolandparvaz, Zexi Zang, Natalia Vapniarsky, Jamal S. Lewis, Kenneth Alvarez, Jasmeen Saini, Judy Van de Water, Rian Harriman
Rok vydání: 2020
Předmět:
02 engineering and technology
Pharmacology
Inbred C57BL
Mice
Epitopes
Engineering
Pregnancy
Nanotechnology
Tissue Distribution
Cells
Cultured
Cultured
biology
Liver Disease
Immunogenicity
Metals and Alloys
Dextrans
MAR autism
Biological Sciences
021001 nanoscience & nanotechnology
Magnetic Resonance Imaging
Toxicity
histopathology
Cytokines
Female
Magnetic Iron Oxide Nanoparticles
medicine.symptom
Antibody
0210 nano-technology
Biotechnology
peptide-functionalized
Biodistribution
Materials science
Cells
0206 medical engineering
Biomedical Engineering
Bioengineering
Inflammation
clearance
Article
Biomaterials
In vivo
distribution
medicine
Animals
Macrophages
Autoantibody
nanoformulation
020601 biomedical engineering
In vitro
Mice
Inbred C57BL
Good Health and Well Being
Chemical Sciences
Ceramics and Composites
biology.protein
Digestive Diseases
Zdroj: Journal of biomedical materials research. Part A, vol 108, iss 5
J Biomed Mater Res A
ISSN: 1552-4965
1549-3296
Popis: In pursuit of a preventive therapeutic for maternal autoantibody-related (MAR) autism, we assessed the toxicity, biodistribution, and clearance of a MAR specific peptide-functionalized dextran iron oxide nanoparticle system in pregnant murine dams. We previously synthesized ~15 nm citrate-coated dextran iron oxide nanoparticles (DIONPs), surface-modified with polyethylene glycol and MAR peptides to produce systems for nanoparticle-based autoantibody reception and entrapments (SNAREs). First, we investigated their immunogenicity and MAR lactate dehydrogenase B antibody uptake in murine serum in vitro. To assess biodistribution and toxicity, as well as systemic effects, we performed in vivo clinical and post mortem pathological evaluations. We observed minimal production of inflammatory cytokines—interleukin 10 (IL-10) and IL-12 following in vitro exposure of macrophages to SNAREs. We established the maximum tolerated dose of SNAREs to be 150 mg/kg at which deposition of iron was evident in the liver and lungs by histology and magnetic resonance imaging but no concurrent evidence of liver toxicity or lung infarction was detected. Further, SNAREs exhibited slower clearance from the maternal blood in pregnant dams compared to DIONPs based on serum total iron concentration. These findings demonstrated that the SNAREs have a prolonged presence in the blood and are safe for use in pregnant mice as evidenced by no associated organ damage, failure, inflammation, and fetal mortality. Determination of the MTD dose sets the basis for future studies investigating the efficacy of our nanoparticle formulation in a MAR autism mouse model.
Databáze: OpenAIRE
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