title: Hyperthermia of magnetic nanoparticles allows passage of sodium fluorescein and Evans blue dye across the blood-retinal barrier.
abstract: The blood-retina barrier (BRB) is a biological barrier consisting of tightly interconnected endothelial cells inside the retinal vascular network that protects the neural tissue from harmful pathogens and neurotoxic molecules circulating in the bloodstream. Unfortunately, with regard to retinoblastoma, this barrier also prevents systemically administered therapeutics reaching the retinal tissue. In this study we introduce a novel technique to locally and transiently increase BRB permeability for drug delivery using hyperthermia of magnetic nanoparticles (MNPs).
  
  
  
  An alternating current (AC) magnetic field was used to induce hyperthermia of locally injected MNPs in the left ophthalmic artery of a rat model. To improve adherence on the surface of the endothelium, commercially available MNPs coated with human transferrin glycoproteins were used. After hyperthermia we assessed the extravasation of systemically injected sodium fluorescein (NaF) as well as Evans blue dye (EBD) into the retinal tissue.
  
  
  
  Spectrofluorometry and fluorescent microscopy image analysis show a significant increase of dye penetration in the retina where hyperthermia of MNPs was applied.
  
  
  
  Our proposed new technique can allow both small and large dye molecules to cross the BRB. While the results are preliminary and thorough evaluation of the retinal tissue following hyperthermia is necessary, this technique has the potential to be an effective mean for the treatment of various diseases such as retinoblastoma.
authors.affiliation: a Institute of Biomedical Engineering, École Polytechnique de Montréal , Montréal , Canada ;|b Department of Pharmacology, Faculty of Medicine , Université de Montréal , Montréal , Canada ;
authors.forename: Seyed Nasrollah
authors.initials: SN
authors.lastname: Tabatabaei
authors.affiliation: a Institute of Biomedical Engineering, École Polytechnique de Montréal , Montréal , Canada ;|b Department of Pharmacology, Faculty of Medicine , Université de Montréal , Montréal , Canada ;
authors.forename: Maryam Sadat
authors.initials: MS
authors.lastname: Tabatabaei
authors.affiliation: b Department of Pharmacology, Faculty of Medicine , Université de Montréal , Montréal , Canada ;
authors.forename: Hélène
authors.initials: H
authors.lastname: Girouard
authors.affiliation: a Institute of Biomedical Engineering, École Polytechnique de Montréal , Montréal , Canada ;|c Department of Medical Nanorobotics, Nanorobotics Laboratory , Montreal , Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Martel
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000378:metabolism*; D004396:Coloring Agents / Q000008:administration & dosage*; D005070:Evans Blue / Q000008:administration & dosage*; D019793:Fluorescein / Q000008:administration & dosage*; D006979:Hyperthermia, Induced; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D008297:Male; D051381:Rats
chemical_list: D004396:Coloring Agents; D058185:Magnetite Nanoparticles; D005070:Evans Blue; D019793:Fluorescein
keywords: AC heating; CNS drug delivery; blood–retinal barrier; hyperthermia; magnetic nanoparticles