Long term in vivo biotransformation of iron oxide nanoparticles

Lévy, Michael; Luciani, Nathalie; Alloyeau, Damien; Elgrabli, Dan; Deveaux, Vanessa; Péchoux, Christine; Chat, Sophie; Wang, Guillaume; Vats, Nidhi; Giligny, François; Factor, Cécile; Lotersztajn, Sophie; Luciani, Alain; Wilhelm, Claire; Gazeau, Florence

doi:10.1016/j.biomaterials.2011.02.031

Cited by 323 publications

(323 citation statements)

References 39 publications

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“…Although there are some previous studies of in vivo MNP distribution and clearance [21,52,55,56], little is known of the route of nanoparticle elimination. Very small amounts of iron are typically lost from normal hepatocytes.…”

Section: Mnp Eliminationmentioning

confidence: 99%

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

Mejías

Gutiérrez

Salas

et al. 2013

Journal of Controlled Release

122

106

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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 nanoparticles effects in vitro on NCTC 1469 nonparenchymal 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 was 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 nonsuperparamagnetic iron forms, with no significant signs of toxicity.

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Section: Mnp Eliminationmentioning

confidence: 99%

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

Mejías

Gutiérrez

Salas

et al. 2013

Journal of Controlled Release

122

106

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“…Both the magnetite and PLGA form harmless degradation products and are cleared from the body via natural pathways 32 . The biodegradable nature of the SPIONs means any cytotoxic effects will diminish with time, but also limits the potential applications to those that do not require cells to maintain their magnetic properties beyond a few months.…”

Section: Discussionmentioning

confidence: 99%

Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles

Tefft

Uthamaraj

Harburn

et al. 2015

JoVE

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Targeted delivery of cells and therapeutic agents would benefit a wide range of biomedical applications by concentrating the therapeutic effect at the target site while minimizing deleterious effects to off-target sites. Magnetic cell targeting is an efficient, safe, and straightforward delivery technique. Superparamagnetic iron oxide nanoparticles (SPION) are biodegradable, biocompatible, and can be endocytosed into cells to render them responsive to magnetic fields. The synthesis process involves creating magnetite (Fe 3 O 4 ) nanoparticles followed by high-speed emulsification to form a poly(lactic-co-glycolic acid) (PLGA) coating. The PLGA-magnetite SPIONs are approximately 120 nm in diameter including the approximately 10 nm diameter magnetite core. When placed in culture medium, SPIONs are naturally endocytosed by cells and stored as small clusters within cytoplasmic endosomes. These particles impart sufficient magnetic mass to the cells to allow for targeting within magnetic fields. Numerous cell sorting and targeting applications are enabled by rendering various cell types responsive to magnetic fields. SPIONs have a variety of other biomedical applications as well including use as a medical imaging contrast agent, targeted drug or gene delivery, diagnostic assays, and generation of local hyperthermia for tumor therapy or tissue soldering. Video LinkThe video component of this article can be found at

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“…This behavior can be assigned to the corrosion behavior in the extremely acid lysosomes, resulting in the exfoliation of the organic protective layer on the nanoprobes. [42][43][44] To assess the small size effect of the synthesized Fe 3 O 4 @P-NPO/ PEG-Glc@Ce6 nanoprobes on cells, confocal images were obtained and flow cytometry was carried out. It is widely accepted that particle size has a key role in targeting cell interaction and endocytosis.…”

Section: Photodynamic Therapy Of Ultra-small Fe 3 O 4 @Polymer-npo/pementioning

confidence: 99%

In vivo high-efficiency targeted photodynamic therapy of ultra-small Fe3O4@polymer-NPO/PEG-Glc@Ce6 nanoprobes based on small size effect

Yin

Zhang

et al. 2017

NPG Asia Mater

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Effectively prolonging the residence time of nanoprobes in the tumor region and reducing the accumulation of nanoprobes in the vital organs (for example, lung, liver and spleen) is crucial for high-efficiency photodynamic therapy (PDT) of cancer. Herein, we systematically report an ultra-small and highly stable nanoplatform with diameters of 4, 8 and 13 nm that exhibited excellent photodynamic therapeutic efficacy using Fe 3 O 4 @polymer-NPO/PEG-Glc@Ce6 nanoprobes. Based on the small size effect, the nanoprobes displayed lower cytotoxicity and excellent biocompatibility. Owing to the synergistic virtues of markedly active targeting and intrinsic small size effect, the Fe 3 O 4 @P-NPO/PEG-Glc@Ce6 nanoprobes can effectively prolong their residence time in the tumor region and reduce accumulation in the normal organs. Benefitting from the small size effect, the synthesized Fe 3 O 4 @P-NPO/PEG-Glc@Ce6 nanoprobes exhibited excellent tumor-targeting capability and photodynamic therapeutic efficacy by inhibiting the growth of tumors in mice under visible red light irradiation with a relatively lower power. The successful application of the small size effect in Fe 3 O 4 @P-NPO/PEG-Glc@Ce6 nanoprobes to significantly improve the PDT efficiency in our strategy suggests new building blocks for PDT of tumors and paves a new way for clinical therapies and translation in the near future.

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Long term in vivo biotransformation of iron oxide nanoparticles

Cited by 323 publications

References 39 publications

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles

In vivo high-efficiency targeted photodynamic therapy of ultra-small Fe3O4@polymer-NPO/PEG-Glc@Ce6 nanoprobes based on small size effect

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