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Fig 1.

X-Ray diffraction pattern of citrate-coated iron oxide nanoparticles.

Black peaks represent citrate-coated IONps and red peaks, ICSD-data base.

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Fig 2.

TEM images and size distribution of the magnetite nanoparticle (IONps).

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Fig 3.

Magnetization as a function of applied field measured at room temperature (IONps).

Low field behavior is shown in the inset.

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Fig 4.

Cell viability after 72-h-exposition to citrate-coated IONps and doxorubicin hydrochloride.

The human HepG2 (hepatocellular carcinoma, A) and HaCaT (spontaneously transformed keratinocytes, B) cell lines were treated with different concentrations (100 to 0.1 ug/mL) of citrate-coated IONps, and the viability was measured 72h later with MTT assay. The blue line represents the nanoparticle and the black line corresponds to doxorubicin hydrochloride (positive control).

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Fig 5.

Average body weight of female Sprague-Dawley rats during the acute oral toxicity experiment.

Results were expressed as mean ± standard deviation; Groups: control (filtered water, 2 ml/animal, n = 4), citrate-coated IONps (diluted in filtered water, 2000 mg/kg, 2 ml/animal, n = 4). Statistical analysis by Student’s T test (* p < 0.05) relating to the control group.

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Table 1.

Relative weight (% relative to final body weight) of heart, kidney, spleen, liver, lung and brain at day 14 of the acute oral toxicity experiment with citrate-coated IONps.

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Fig 6.

Evaluation of (A) Creatinine and (B) ALT plasma levels at the 14-day of the acute oral toxicity experiment of citrate-coated IONps. Results were expressed as mean ± standard deviation; Animals: female Sprague-Dawley rats (6 to 8 weeks, weighing between 200 ± 60 g); Groups: Pre (animals before citrate-coated IONps treatment, n = 4), Post (animals at the 14-day after citrate-coated IONps treatment, n = 4). Statistical analysis by Student’s T test (* p < 0.05) relating to the basal evaluation.

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Table 2.

Biochemical plasma parameters at days 0 (baseline/pre-treatment) and 14 (post-treatment) of the acute oral toxicity protocols using citrate-coated IONps.

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Fig 7.

Photomicrograph of spleen section of H&E staining of Sprague-Dawley.

(A, B) spleen, (C, D) liver, (E, F) brain, (G, H) heart, (I,J) lung and (K, L) kidney. Animals: female Sprague-Dawley rats (6 to 8 weeks, weighing between 200 ± 60 g); A, C, E, G, I and K: control group (filtered water, 2 ml/animal, n = 4); B, D, F, H, J and L: citrate-coated IONps group (diluted in filtered water, 2000 mg/kg, 2 ml/animal, n = 4). Scale bar: 50μm, 10x magnification.

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Fig 8.

Fe concentration analysis by Graphite Furnace Atomic Spectrometry in liver at 14-day of the acute oral toxicity experiment of the citrate-coated IONps.

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Fig 9.

Fe concentration analysis by Prussian blue staining in spleen (A, C) and liver (B, D) at 14-day of the acute oral toxicity experiment of the citrate-coated IONps. Animals: female Sprague-Dawley rats (6 to 8 weeks, weighing between 200 ± 60 g); A and B: control group (potable water, 2 ml/animal, n = 4); C and D: citrate-coated IONps group (diluted in potable water, 2000 mg/kg, 2 ml/animal, n = 4). Scale bar: 50μm, 20x magnification. Note that Fe stained by Prussian blue in liver (circle and arrow) is lower concentration then spleen.

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Fig 10.

Number of Prussian blue positive profiles after exposure to citrate-coated IONps.

The graphs show quantification of the average number of Prussian blue positive staining per section from Sprague-Dawley administered control (vehicle) and treated (citrate-coated IONps). A: Liver; B: Spleen. Statistical analysis by Student’s T test (* p < 0.05) relating to the control group.

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Table 3.

Iron concentration analysis by Graphite Furnace Atomic Spectrometry in vital organs at day 14 of the acute oral toxicity experiment with citrate-coated IONps.

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