title: Iron oxide nanoparticles for neuronal cell applications: uptake study and magnetic manipulations.
abstract: BACKGROUND
  The ability to direct and manipulate neuronal cells has important potential in therapeutics and neural network studies. An emerging approach for remotely guiding cells is by incorporating magnetic nanoparticles (MNPs) into cells and transferring the cells into magnetic sensitive units. Recent developments offer exciting possibilities of magnetic manipulations of MNPs-loaded cells by external magnetic fields. In the present study, we evaluated and characterized uptake properties for optimal loading of cells by MNPs. We examined the interactions between MNPs of different cores and coatings, with primary neurons and neuron-like cells.
  
  
  RESULTS
  We found that uncoated-maghemite iron oxide nanoparticles maximally interact and penetrate into cells with no cytotoxic effect. We observed that the cellular uptake of the MNPs depends on the time of incubation and the concentration of nanoparticles in the medium. The morphology patterns of the neuronal cells were not affected by MNPs uptake and neurons remained electrically active. We theoretically modeled magnetic fluxes and demonstrated experimentally the response of MNP-loaded cells to the magnetic fields affecting cell motility. Furthermore, we successfully directed neurite growth orientation along regeneration.
  
  
  CONCLUSIONS
  Applying mechanical forces via magnetic mediators is a useful approach for biomedical applications. We have examined several types of MNPs and studied the uptake behavior optimized for magnetic neuronal manipulations.
authors.affiliation: Neuro-engineering lab, Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.|Bar Ilan Institute of Nanotechnologies and Advanced Materials, Ramat Gan, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Marcus
authors.affiliation: Neuro-engineering lab, Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.|Bar Ilan Institute of Nanotechnologies and Advanced Materials, Ramat Gan, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Karni
authors.affiliation: Neuro-engineering lab, Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.|Bar Ilan Institute of Nanotechnologies and Advanced Materials, Ramat Gan, Israel.
authors.forename: Koby
authors.initials: K
authors.lastname: Baranes
authors.affiliation: Department of Chemistry, Bar Ilan University, Ramat Gan, Israel.|Bar Ilan Institute of Nanotechnologies and Advanced Materials, Ramat Gan, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Levy
authors.affiliation: Neuro-engineering lab, Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.|Bar Ilan Institute of Nanotechnologies and Advanced Materials, Ramat Gan, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Alon
authors.affiliation: Department of Chemistry, Bar Ilan University, Ramat Gan, Israel.|Bar Ilan Institute of Nanotechnologies and Advanced Materials, Ramat Gan, Israel.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Margel
authors.affiliation: Neuro-engineering lab, Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel. orit.shefi@biu.ac.il.|Bar Ilan Institute of Nanotechnologies and Advanced Materials, Ramat Gan, Israel. orit.shefi@biu.ac.il.
authors.forename: Orit
authors.initials: O
authors.lastname: Shefi
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005290:Ferric Compounds / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity; D060526:Magnetic Fields; D008280:Magnetics / Q000379:methods; D058185:Magnetite Nanoparticles / Q000032:analysis* / Q000627:therapeutic use / Q000633:toxicity; D008846:Micromanipulation / Q000379:methods; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D051381:Rats
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide
keywords: Cell positioning; Guidance; Magnetic field; Magnetic nanoparticles; Neuronal cells; Neuronal regeneration; Uptake