title: Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties.
abstract: Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe₃O₄-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol (EG), respectively. They were systematically investigated by means of X-ray diffraction, transmission electron microscopy and vibration sample magnetometry. Hyperthermia measurements showed that Specific Absorption Rate (SAR) dependence on the external alternating magnetic field amplitude (up to 65 kA/m, 355 kHz) presented a sigmoidal shape, with remarkable SAR saturation values of ~1400 W/gMNPfor the small monocrystalline MNPs and only 400 W/gMNPfor the large polycrystalline MNPs, in water. SAR values were slightly reduced in cell culture media, but decreased one order of magnitude in highly viscous PEG1000. Toxicity assays performed on four cell lines revealed almost no toxicity for the small MNPs and a very small level of toxicity for the large MNPs, up to a concentration of 0.2 mg/mL. Cellular uptake experiments revealed that both MNPs penetrated the cells through endocytosis, in a time dependent manner and escaped the endosomes with a faster kinetics for large MNPs. Biodegradation of large MNPs inside cells involved an all-or-nothing mechanism.
authors.affiliation: Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur 6, 400349 Cluj-Napoca, Romania. cristian.iacovita@umfcluj.ro.
authors.forename: Cristian
authors.initials: C
authors.lastname: Iacovita
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Medicine, ''Iuliu Hatieganu'' University of Medicine and Pharmacy, Pasteur 6, 400349 Cluj-Napoca, Romania. aflorea@umfcluj.ro.
authors.forename: Adrian
authors.initials: A
authors.lastname: Florea
authors.affiliation: Faculty of Physics, "Babes Bolyai" University, Kogalniceanu 1, 400084 Cluj-Napoca, Romania. roxana.pacurariu@phys.ubbcluj.ro.
authors.forename: Roxana
authors.initials: R
authors.lastname: Dudric
authors.affiliation: Department of Reproduction Obstetrics and Veterinary Gynecology, University of Agricultural Sciences and Veterinary Medicine, Manastur 3-5, 400372 Cluj-Napoca, Romania. pallemoke@gmail.com.
authors.forename: Emoke
authors.initials: E
authors.lastname: Pall
authors.affiliation: Department of Bionanoscopy, MedFuture Research Center for Advance Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur 4-6, 400337 Cluj-Napoca, Romania. alin.moldovan@umfcluj.ro.
authors.forename: Alin Iulian
authors.initials: AI
authors.lastname: Moldovan
authors.affiliation: Faculty of Physics, "Babes Bolyai" University, Kogalniceanu 1, 400084 Cluj-Napoca, Romania. romulus.tetean@phys.ubbcluj.ro.
authors.forename: Romulus
authors.initials: R
authors.lastname: Tetean
authors.affiliation: Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur 6, 400349 Cluj-Napoca, Romania. rares.stiufiuc@umfcluj.ro.|Department of Bionanoscopy, MedFuture Research Center for Advance Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur 4-6, 400337 Cluj-Napoca, Romania. rares.stiufiuc@umfcluj.ro.
authors.forename: Rares
authors.initials: R
authors.lastname: Stiufiuc
authors.affiliation: Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, Pasteur 6, 400349 Cluj-Napoca, Romania. clucaciu@umfcluj.ro.
authors.forename: Constantin Mihai
authors.initials: CM
authors.lastname: Lucaciu
mesh_terms: D000327:Adsorption; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019855:Ethylene Glycol / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D011092:Polyethylene Glycols; D019855:Ethylene Glycol
keywords: biodegradation; cancer cells uptake; endocytosis; large magnetic nanoparticles; magnetic hyperthermia; polyethylene glycol; polyhedral iron oxide magnetic nanoparticles; specific absorption rate