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 |
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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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