title: Targeting intracellular compartments by magnetic polymeric nanoparticles.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) show a great promise for a wide specter of bioapplications, due to their characteristic magnetic properties exhibited only in the presence of magnetic field. Their advantages in the fields of magnetic drug targeting and imaging are well established and their safety is assumed, since iron oxide nanoparticles have already been approved for in vivo application, however, according to many literature reports the bare metal oxide nanoparticles may cause toxic effects on treated cells. Therefore, it is reasonable to prevent the direct interactions between metal oxide core and surrounding environment. In the current research ricinoleic acid coated maghemite nanoparticles were successfully synthesized, characterized and incorporated in the polymeric matrix, resulting in nanosized magnetic polymeric particles. The carrier system was shown to exhibit superparamagnetic properties and was therefore responsive towards external magnetic field. Bioevaluation using T47-D breast cancer cells confirmed internalization of magnetic polymeric nanoparticles (MNPs) and their intracellular localization in various subcellular compartments, depending on presence/absence of external magnetic field. However, the number of internalized MNPs observed by fluorescent and transmission electron microscopy was relatively low, making such way of targeting effective only for delivery of highly potent drugs. The scanning electron microscopy of treated cells revealed that MNPs influenced the cell adhesion, when external magnetic field was applied, and that treatment resulted in damaged apical plasma membrane right after exposure to the magnetic carrier. On the other hand, MNPs showed only reversibly reduced cellular metabolic activity in concentrations up to 200 μg/ml and, in the tested concentration the cell cycle distribution was within the normal range, indicating safety of the established magnetic carrier system for the treated cells.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia. kocbekp@ffa.uni-lj.si
authors.forename: Petra
authors.initials: P
authors.lastname: Kocbek
authors.forename: Slavko
authors.initials: S
authors.lastname: Kralj
authors.forename: Mateja Erdani
authors.initials: ME
authors.lastname: Kreft
authors.forename: Julijana
authors.initials: J
authors.lastname: Kristl
mesh_terms: D018929:Cell Culture Techniques; D002453:Cell Cycle; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D064347:Microscopy, Electrochemical, Scanning; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D010316:Particle Size; D010873:Pinocytosis; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012277:Ricinoleic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013499:Surface Properties
chemical_list: D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D012277:Ricinoleic Acids; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C030521:ricinoleic acid
keywords: Emulsion solvent evaporation method; Magnetic targeting; Nanoparticles; PLGA; Superparamagnetic iron oxide