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Evaluation of iron oxide nanoparticle biocompatibility

Identifieur interne : 000426 ( Pmc/Curation ); précédent : 000425; suivant : 000427

Evaluation of iron oxide nanoparticle biocompatibility

Auteurs : Amel Hanini [France, Tunisie] ; Alain Schmitt [France] ; Kamel Kacem [Tunisie] ; François Chau [France] ; Souad Ammar [France] ; Julie Gavard [France]

Source :

RBID : PMC:3090275

Abstract

Nanotechnology is an exciting field of investigation for the development of new treatments for many human diseases. However, it is necessary to assess the biocompatibility of nanoparticles in vitro and in vivo before considering clinical applications. Our characterization of polyol-produced maghemite γ-Fe2O3 nanoparticles showed high structural quality. The particles showed a homogeneous spherical size around 10 nm and could form aggregates depending on the dispersion conditions. Such nanoparticles were efficiently taken up in vitro by human endothelial cells, which represent the first biological barrier to nanoparticles in vivo. However, γ-Fe2O3 can cause cell death within 24 hours of exposure, most likely through oxidative stress. Further in vivo exploration suggests that although γ-Fe2O3 nanoparticles are rapidly cleared through the urine, they can lead to toxicity in the liver, kidneys and lungs, while the brain and heart remain unaffected. In conclusion, γ-Fe2O3 could exhibit harmful properties and therefore surface coating, cellular targeting, and local exposure should be considered before developing clinical applications.


Url:
DOI: 10.2147/IJN.S17574
PubMed: 21589646
PubMed Central: 3090275

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PMC:3090275

Le document en format XML

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<p>Nanotechnology is an exciting field of investigation for the development of new treatments for many human diseases. However, it is necessary to assess the biocompatibility of nanoparticles in vitro and in vivo before considering clinical applications. Our characterization of polyol-produced maghemite γ-Fe
<sub>2</sub>
O
<sub>3</sub>
nanoparticles showed high structural quality. The particles showed a homogeneous spherical size around 10 nm and could form aggregates depending on the dispersion conditions. Such nanoparticles were efficiently taken up in vitro by human endothelial cells, which represent the first biological barrier to nanoparticles in vivo. However, γ-Fe
<sub>2</sub>
O
<sub>3</sub>
can cause cell death within 24 hours of exposure, most likely through oxidative stress. Further in vivo exploration suggests that although γ-Fe
<sub>2</sub>
O
<sub>3</sub>
nanoparticles are rapidly cleared through the urine, they can lead to toxicity in the liver, kidneys and lungs, while the brain and heart remain unaffected. In conclusion, γ-Fe
<sub>2</sub>
O
<sub>3</sub>
could exhibit harmful properties and therefore surface coating, cellular targeting, and local exposure should be considered before developing clinical applications.</p>
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<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Int J Nanomedicine</journal-id>
<journal-title-group>
<journal-title>International Journal of Nanomedicine</journal-title>
</journal-title-group>
<issn pub-type="ppub">1176-9114</issn>
<issn pub-type="epub">1178-2013</issn>
<publisher>
<publisher-name>Dove Medical Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">21589646</article-id>
<article-id pub-id-type="pmc">3090275</article-id>
<article-id pub-id-type="doi">10.2147/IJN.S17574</article-id>
<article-id pub-id-type="publisher-id">ijn-6-787</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Evaluation of iron oxide nanoparticle biocompatibility</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Hanini</surname>
<given-names>Amel</given-names>
</name>
<xref ref-type="aff" rid="af1-ijn-6-787">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="af2-ijn-6-787">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="af3-ijn-6-787">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="af4-ijn-6-787">
<sup>4</sup>
</xref>
<xref ref-type="aff" rid="af5-ijn-6-787">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schmitt</surname>
<given-names>Alain</given-names>
</name>
<xref ref-type="aff" rid="af2-ijn-6-787">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="af3-ijn-6-787">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="af4-ijn-6-787">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kacem</surname>
<given-names>Kamel</given-names>
</name>
<xref ref-type="aff" rid="af5-ijn-6-787">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chau</surname>
<given-names>François</given-names>
</name>
<xref ref-type="aff" rid="af1-ijn-6-787">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="af2-ijn-6-787">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ammar</surname>
<given-names>Souad</given-names>
</name>
<xref ref-type="aff" rid="af1-ijn-6-787">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="af2-ijn-6-787">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gavard</surname>
<given-names>Julie</given-names>
</name>
<xref ref-type="aff" rid="af2-ijn-6-787">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="af3-ijn-6-787">
<sup>3</sup>
</xref>
<xref ref-type="aff" rid="af4-ijn-6-787">
<sup>4</sup>
</xref>
<xref ref-type="corresp" rid="c1-ijn-6-787"></xref>
</contrib>
</contrib-group>
<aff id="af1-ijn-6-787">
<label>1</label>
Interface Traitement, Organisation et Dynamique des Systèmes (ITODYS), Université Paris 7, Paris, France;</aff>
<aff id="af2-ijn-6-787">
<label>2</label>
CNRS, Paris, France;</aff>
<aff id="af3-ijn-6-787">
<label>3</label>
Inserm, Paris, France;</aff>
<aff id="af4-ijn-6-787">
<label>4</label>
Univ Paris Descartes, Paris, France;</aff>
<aff id="af5-ijn-6-787">
<label>5</label>
Universite de Carthage, Jarzouna, Tunisia</aff>
<author-notes>
<corresp id="c1-ijn-6-787">Correspondence: Julie Gavard, Institut Cochin, 22 Rue Mechain, Rm 306, 75014 Paris, France, Tel +33 1 4051 6424, Fax +33 1 4051 6430, Email
<email>julie.gavard@inserm.fr</email>
</corresp>
</author-notes>
<pub-date pub-type="collection">
<year>2011</year>
</pub-date>
<pmc-comment>Dove Press titles changed from ppub to collections in 2009. Fake ppub written to satisfy Coll Date Type=ppub</pmc-comment>
<pub-date pub-type="ppub">
<year>2011</year>
</pub-date>
<pub-date pub-type="epub">
<day>14</day>
<month>4</month>
<year>2011</year>
</pub-date>
<volume>6</volume>
<fpage>787</fpage>
<lpage>794</lpage>
<history>
<date date-type="received">
<day>13</day>
<month>4</month>
<year>2011</year>
</date>
</history>
<permissions>
<copyright-statement>© 2011 Hanini et al, publisher and licensee Dove Medical Press Ltd.</copyright-statement>
<copyright-year>2011</copyright-year>
<license>
<license-p>This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<p>Nanotechnology is an exciting field of investigation for the development of new treatments for many human diseases. However, it is necessary to assess the biocompatibility of nanoparticles in vitro and in vivo before considering clinical applications. Our characterization of polyol-produced maghemite γ-Fe
<sub>2</sub>
O
<sub>3</sub>
nanoparticles showed high structural quality. The particles showed a homogeneous spherical size around 10 nm and could form aggregates depending on the dispersion conditions. Such nanoparticles were efficiently taken up in vitro by human endothelial cells, which represent the first biological barrier to nanoparticles in vivo. However, γ-Fe
<sub>2</sub>
O
<sub>3</sub>
can cause cell death within 24 hours of exposure, most likely through oxidative stress. Further in vivo exploration suggests that although γ-Fe
<sub>2</sub>
O
<sub>3</sub>
nanoparticles are rapidly cleared through the urine, they can lead to toxicity in the liver, kidneys and lungs, while the brain and heart remain unaffected. In conclusion, γ-Fe
<sub>2</sub>
O
<sub>3</sub>
could exhibit harmful properties and therefore surface coating, cellular targeting, and local exposure should be considered before developing clinical applications.</p>
</abstract>
<kwd-group>
<kwd>nanoparticles</kwd>
<kwd>polyol process</kwd>
<kwd>endothelial cell</kwd>
<kwd>cytotoxicity</kwd>
<kwd>clearance</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group>
<fig id="f1-ijn-6-787" position="float">
<label>Figure 1</label>
<caption>
<p>Nanoparticles exhibit spherical shapes.
<bold>A</bold>
) Polyol-made iron oxide powder consists of maghemite nanocrystals as shown by their broadened X-ray diffraction pattern.
<bold>B</bold>
) Fe
<sub>2</sub>
O
<sub>3</sub>
iron oxide nanoparticle morphology was observed by transmission electron microscopy on a collection of as-produced particles (left image). A zoom on one representative particle is shown (right panel).</p>
</caption>
<graphic xlink:href="ijn-6-787f1"></graphic>
</fig>
<fig id="f2-ijn-6-787" position="float">
<label>Figure 2</label>
<caption>
<p>Nanoparticle internalization in human endothelial cells.
<bold>A</bold>
and
<bold>B</bold>
) Human umbilical vein endothelial cells (HUVEC) were incubated with FITC-labelled nanoparticle (NP, 10 μg/mL, green) for the indicated times in serum-free medium. Nuclei were counterstained with 4,6-diamidino-2-phenylindole (DAPI) (blue) and samples were analyzed by confocal microscopy.</p>
</caption>
<graphic xlink:href="ijn-6-787f2"></graphic>
</fig>
<fig id="f3-ijn-6-787" position="float">
<label>Figure 3</label>
<caption>
<p>Subcellular localization of nanoparticles. Transmission electron microscopy was performed on human umbilical vascular endothelial cells (HUVEC) exposed to nanoparticles for the indicated times.</p>
</caption>
<graphic xlink:href="ijn-6-787f3"></graphic>
</fig>
<fig id="f4-ijn-6-787" position="float">
<label>Figure 4</label>
<caption>
<p>Effect of nanoparticles on endothelial cell viability.
<bold>A</bold>
) The number of viable cells was measured by 3-(4,5-dimethylthiazol-2-yl) diphenyltetrazolium bromide (MTT) when exposed to nanoparticles (NP) at the indicated times and concentrations. Results were expressed as a ratio to nonstimulated serum-free cultured cells for each time point.
<bold>B</bold>
) Cell toxicity was evaluated by LDH leakage and calculated as described in the method section, in human umbilical vein endothelial cells (HUVEC) exposed to 10 μg/mL of NP.
<bold>C</bold>
) Cells exposed to 10 μg/mL of NP were harvested for Western blot analysis at the indicated time points. Phosphorylation (p) of Akt and endothelial nitric oxide synthase (eNOS) was monitored, along with Akt, eNOS and Caspase 3.
<bold>D</bold>
) Reactive oxygen species (ROS) production was examined in NP (10 μg/mL)-exposed HUVEC at the indicated time points. Fluorescence values were normalized to the ones obtained in control conditions.</p>
<p>
<bold>Notes:</bold>
All results are representative of three independent experiments, **
<italic>P</italic>
< 0.01; *
<italic>P</italic>
< 0.05.</p>
</caption>
<graphic xlink:href="ijn-6-787f4"></graphic>
</fig>
<fig id="f5-ijn-6-787" position="float">
<label>Figure 5</label>
<caption>
<p>In vivo clearance and toxicity of nanoparticles. Six animals for each groups received saline (Sham) or nanoparticle (NP) (0.8 mg/kg NP) by intravenous injection.
<bold>A</bold>
and
<bold>B</bold>
) Blood and urine clearance profile of fluorescein isothiocyanate (FITC)-labeled NP was measured either by flow cytometry or spectrophotometry, respectively, after 24 and 72 hours.
<bold>C</bold>
) Animals were weighed during the course of control and NP treatment.
<bold>D</bold>
) Numbers of white and red blood cells (WBC, RBC) were examined in animals treated with control and NP for 14 days.
<bold>E</bold>
) Organs were collected 14 days post-treatment and processed for staining with hematoxylin and eosin.</p>
<p>
<bold>Notes:</bold>
**
<italic>P</italic>
< 0.01; *
<italic>P</italic>
< 0.05.</p>
</caption>
<graphic xlink:href="ijn-6-787f5"></graphic>
</fig>
<table-wrap id="t1-ijn-6-787" position="float">
<label>Table 1</label>
<caption>
<p>Physical properties of iron oxide nanoparticle</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="1" colspan="1">
<bold>Solution</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><
<bold>D
<sub>DLS</sub>
> (nm)</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1">
<bold>Zeta potential (mv)</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1">
<bold>Conductivity (ms/cm)</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1">
<bold>Effective voltage (V)</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Distilled water</td>
<td align="left" valign="top" rowspan="1" colspan="1">2420</td>
<td align="left" valign="top" rowspan="1" colspan="1">+12.8</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">PBS solution</td>
<td align="left" valign="top" rowspan="1" colspan="1">204</td>
<td align="left" valign="top" rowspan="1" colspan="1">−23.6</td>
<td align="left" valign="top" rowspan="1" colspan="1">15.7</td>
<td align="left" valign="top" rowspan="1" colspan="1">49.5</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">DMEM</td>
<td align="left" valign="top" rowspan="1" colspan="1">90</td>
<td align="left" valign="top" rowspan="1" colspan="1">−9.1</td>
<td align="left" valign="top" rowspan="1" colspan="1">14.3</td>
<td align="left" valign="top" rowspan="1" colspan="1">49.5</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="1" colspan="1">Saline solution</td>
<td align="left" valign="top" rowspan="1" colspan="1">198</td>
<td align="left" valign="top" rowspan="1" colspan="1">−23.3</td>
<td align="left" valign="top" rowspan="1" colspan="1">8.7</td>
<td align="left" valign="top" rowspan="1" colspan="1">48.6</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn1-ijn-6-787">
<p>
<bold>Notes:</bold>
Average hydrodynamic diameter (DLS), zeta potential, electric conductivity and voltage of produced iron oxide particles were measured when dispersed in distilled water, PBS and DMEM liquids.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>

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