title: The role of ROS generation from magnetic nanoparticles in an alternating magnetic field on cytotoxicity.
abstract: Monosaccharide coated iron oxide nanoparticles were developed to selectively target colon cancer cell lines for magnetically mediated energy delivery therapy. The nanoparticles were prepared using a coupling reaction to attach the glucose functional group to the iron oxide core, and functionality was confirmed with physicochemical characterization techniques. The targeted nanoparticles were internalized into CT26 cells at a greater extent than non-targeted nanoparticles, and the nanoparticles were shown to be localized within lysosomes. Cells with internalized nanoparticles were exposed to an AMF to determine the potential to delivery therapy. Cellular ROS generation and apoptotic cell death was enhanced with field exposure. The nanoparticle coatings inhibit the Fenton-like surface generation of ROS suggesting a thermal or mechanical effect is more likely the source of the intracellular effect, unless the nanoparticle coating is unstable in the cellular environment.
  
  
  CONCLUSIONS
  This is the first study to assess glucose coated MNPs for the delivery of MagMED therapy. With exposure of an AMF, the glucose-coated nanoparticles displayed a significant increase in cellular ROS and apoptotic cell death with no measurable increase in media temperature. To determine the mechanism of toxicity, we investigated the surface generation of ROS through Fenton-like chemistry. The coated systems displayed negligible ROS generation compared to uncoated nanoparticles. These observations suggest the cellular ROS measured is attributed to a thermal or mechanical effect of the internalized nanoparticles. In summary, this manuscript reports on some new insights as to the mechanism of MagMED therapies, which are of high interest to the biomaterials and cancer nanomedicine fields.
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wydra
authors.affiliation: Department of Surgery, College of Medicine, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Piotr G
authors.initials: PG
authors.lastname: Rychahou
authors.affiliation: Department of Surgery, College of Medicine, University of Kentucky, Lexington, KY 40506, USA; Markey Cancer Center, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Kimberly W
authors.initials: KW
authors.lastname: Anderson
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dziubla
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, KY 40506, USA. Electronic address: hilt@engr.uky.edu.
authors.forename: J Zach
authors.initials: JZ
authors.lastname: Hilt
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D019343:Citric Acid / Q000737:chemistry; D000067493:Dynamic Light Scattering; D004705:Endocytosis; D005947:Glucose / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D009005:Monosaccharides / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity
chemical_list: C045076:Fenton's reagent; D058185:Magnetite Nanoparticles; D009005:Monosaccharides; D017382:Reactive Oxygen Species; D019343:Citric Acid; D006861:Hydrogen Peroxide; D007501:Iron; D053148:Caspase 3; D053179:Caspase 7; D005947:Glucose
keywords: Glyconanoparticles; Iron oxide; Magnetically mediated energy delivery; Reactive oxygen species