title: In vivo nanoneurotoxicity screening using oxidative stress and neuroinflammation paradigms.
abstract: Iron oxide nanoparticles (IONPs) are promising neuroimaging agents and molecular cargo across neurovascular barriers. Development of intrinsically safe IONP chemistries requires a robust in vivo nanoneurotoxicity screening model. Herein, we engineered four IONPs of different surface and core chemistries: DMSA-Fe2O3, DMSA-Fe3O4, PEG-Fe3O4 and PEG-Au-Fe3O4. Capitalizing on the ability of the peripheral nervous system to recruit potent immune cells from circulation, we characterized a spatiotemporally controlled platform for the study of in vivo nanobiointerfaces with hematogenous immune cells, neuroglial and neurovascular units after intraneural IONP delivery into rat sciatic nerve. SQUID magnetometry and histological iron stain were used for IONP tracking. Among the IONPs, DMSA-Fe2O3 NPs were potent pro-apoptotic agents in nerve, with differential ability to regulate oxidative stress, inflammation and apoptotic signaling in neuroglia, macrophages, lymphocytes and endothelial cells. This platform aims to facilitate the development of predictive paradigms of nanoneurotoxicity based on mechanistic investigation of relevant in vivo bio-nanointerfaces.
  
  
  BACKGROUND
  This team of investigators report the development of a platform that enables screening of iron oxide nanoparticles from the standpoint of their potential neurotoxicity, utilizing rat sciatic nerves. Such screening tools are clearly needed with the potential advent of iron oxide nanoparticle-based diagnostic and therapeutic approaches.
authors.affiliation: Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA, USA.
authors.forename: Youngsoon
authors.initials: Y
authors.lastname: Kim
authors.forename: Seong Deok
authors.initials: SD
authors.lastname: Kong
authors.forename: Li-Han
authors.initials: LH
authors.lastname: Chen
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pisanic
authors.forename: Sungho
authors.initials: S
authors.lastname: Jin
authors.forename: Veronica I
authors.initials: VI
authors.lastname: Shubayev
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D055598:Chemical Phenomena; D005260:Female; D007249:Inflammation / Q000473:pathology*; D058185:Magnetite Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010641:Phenotype; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D004113:Succimer / Q000737:chemistry; D013499:Surface Properties
chemical_list: D000975:Antioxidants; D058185:Magnetite Nanoparticles; D009498:Neurotoxins; D011092:Polyethylene Glycols; D004113:Succimer
keywords: Blood–brain barrier; Iron oxide; Magnetic nanoparticles; Nanotoxicity; Theranostic