title: Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications.
abstract: Although iron oxide magnetic nanoparticles (MNP) have been proposed for numerous biomedical applications, little is known about their biotransformation and long-term toxicity in the body. Dimercaptosuccinic acid (DMSA)-coated magnetic nanoparticles have been proven efficient for in vivo drug delivery, but these results must nonetheless be sustained by comprehensive studies of long-term distribution, degradation and toxicity. We studied DMSA-coated magnetic nanoparticle effects in vitro on NCTC 1469 non-parenchymal hepatocytes, and analyzed their biodistribution and biotransformation in vivo in C57BL/6 mice. Our results indicate that DMSA-coated magnetic nanoparticles have little effect on cell viability, oxidative stress, cell cycle or apoptosis on NCTC 1469 cells in vitro. In vivo distribution and transformation were studied by alternating current magnetic susceptibility measurements, a technique that permits distinction of MNP from other iron species. Our results show that DMSA-coated MNP accumulate in spleen, liver and lung tissues for extended periods of time, in which nanoparticles undergo a process of conversion from superparamagnetic iron oxide nanoparticles to other non-superparamagnetic iron forms, with no significant signs of toxicity. This work provides the first evidence of DMSA-coated magnetite nanoparticle biotransformation in vivo.
authors.affiliation: Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)/CSIC, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Mejías
authors.forename: Lucía
authors.initials: L
authors.lastname: Gutiérrez
authors.forename: Gorka
authors.initials: G
authors.lastname: Salas
authors.forename: Sonia
authors.initials: S
authors.lastname: Pérez-Yagüe
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Zotes
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Lázaro
authors.forename: María P
authors.initials: MP
authors.lastname: Morales
authors.forename: Domingo F
authors.initials: DF
authors.lastname: Barber
mesh_terms: D000818:Animals; D001711:Biotransformation; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D013154:Spleen / Q000378:metabolism; D004113:Succimer / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D058185:Magnetite Nanoparticles; D004113:Succimer; D007501:Iron; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D005978:Glutathione
keywords: Biocompatibility; Biodistribution; Biotransformation; Cytotoxicity; Iron oxide; Nanoparticle