title: Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery.
abstract: Magnetic targeting is useful for intravascular or intracavitary drug delivery, including tumor chemotherapy or intraocular antiangiogenic therapy. For all such in vivo applications, the magnetic drug carrier must be biocompatible and nontoxic. In this work, we investigated the toxic properties of magnetic nanoparticles coated with polyethylenoxide (PEO) triblock copolymers. Such coatings prevent the aggregation of magnetic nanoparticles and guarantee consistent magnetic and nonmagnetic flow properties. It was found that the PEO tail block length inversely correlates with toxicity. The nanoparticles with the shortest 0.75 kDa PEO tails were the most toxic, while particles coated with the 15 kDa PEO tail block copolymers were the least toxic. Toxicity responses of the tested prostate cancer cell lines (PC3 and C4-2), human umbilical vein endothelial cells (HUVECs), and human retinal pigment epithelial cells (HRPEs) were similar. Furthermore, all cell types took up the coated magnetic nanoparticles. It is concluded that magnetite nanoparticles coated with triblock copolymers containing PEO tail lengths of above 2 kDa are biocompatible and appropriate for in vivo application.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada. uhafeli@interchange.ubc.ca
authors.forename: Urs O
authors.initials: UO
authors.lastname: Häfeli
authors.forename: Judy S
authors.initials: JS
authors.lastname: Riffle
authors.forename: Linda
authors.initials: L
authors.lastname: Harris-Shekhawat
authors.forename: Anita
authors.initials: A
authors.lastname: Carmichael-Baranauskas
authors.forename: Framin
authors.initials: F
authors.lastname: Mark
authors.forename: James P
authors.initials: JP
authors.lastname: Dailey
authors.forename: David
authors.initials: D
authors.lastname: Bardenstein
mesh_terms: D001693:Biological Transport, Active; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects; D052203:Ferrosoferric Oxide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D006801:Humans; D008297:Male; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects
chemical_list: D011092:Polyethylene Glycols; D052203:Ferrosoferric Oxide