Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications
| Autor: | María del Puerto Morales, Teresa M. Zotes, Domingo F. Barber, Lucía Gutiérrez, Gorka Salas, Francisco J. Lázaro, Sonia Pérez-Yagüe, Raquel Mejías |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Biodistribution
Cell Survival Stereochemistry Iron Cytotoxicity Iron oxide Pharmaceutical Science 02 engineering and technology Kidney 010402 general chemistry 01 natural sciences Cell Line Feces Mice chemistry.chemical_compound Nanoparticle Biotransformation In vivo Biotransformations Animals Viability assay Magnetite Nanoparticles Lung Caspase 3 Chemistry Myocardium equipment and supplies 021001 nanoscience & nanotechnology Glutathione 0104 chemical sciences 3. Good health Mice Inbred C57BL Oxidative Stress Liver Toxicity Drug delivery Biophysics Magnetic nanoparticles Female Biocompatibility Mitogen-Activated Protein Kinases Succimer 0210 nano-technology Spleen |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Repositorio Institucional del Instituto Madrileño de Estudios Avanzados en Nanociencia |
| Popis: | 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. RM holds a post-doctoral contract supported by EU-FP7 MULTIFUN project (no. 262943), LG holds a Sara Borrell post-doctoral contract (CD09/00030) from the Carlos III Health Institute, Spanish Ministry for Health, Social Services and Equality (MSSSI), and TMZ received a FPU pre-doctoral fellowship from the Spanish Ministry of Economy and Competitiveness (MINECO). This work was partially supported by grants from the MINECO (SAF-2011-23639 to DFB and MAT2011-23641 and CSD2007-00010 to MPM), the Research Network in Inflammation and Rheumatic Diseases (RIER) of the ISCIII-MSSSI Cooperative Research Thematic Network program (RD08/0075/0015 to DFB), the Madrid regional government (S009/MAT-1726 to MPM), and EU-FP7 MULTIFUN project (no. 262943 to DFB and MPM). S2009/MAT-1726/Nanobiomagnet |
| Databáze: | OpenAIRE |
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