Toxicologic effects of gold nanoparticles in vivo by different administration routes

Figures & data

Figure 1 Size and morphology of gold nanoparticles. The ultraviolet spectra of gold nanoparticles and transmission electron microscopic analysis (figure inset).

Note: Gold nanoparticles were synthesized following the procedure described by Turkevich et al.³⁰

Figure 2 Body weight changes for mice treated with gold nanoparticles at doses of 137.5–2200 μg/kg.

Note: Body weight was measured every two days. Each point represents the mean ± standard deviation of six mice. Data were analyzed by Student’s t-test and the differences between the doses and control group for each organ are not significant (P > 5%).

Figure 3 Body weight changes in mice treated with gold nanoparticles 1100 μg/kg by using three administration routes, ie, oral, intraperitoneal, and tail vein injection.

Note: Each point represents mean ± standard deviation. Data were analyzed by Student’s t-test. *Represents significant difference from the control group (P < 0.05).

Table 1 A summary of in vivo toxicity of gold nanoparticles

Group	Surface coating	Size	Study period	Dose	Method of administration
Hillyer^Citation45	Naked	4, 10, 28, and 58 nm	7 days	20,000 μg/kg	Oral
Hainfeld^Citation10	PBS buffered	1.9 nm	5 min	1350 μg/kg	Tail vein
de Jong^Citation32	Naked	10, 50, 100, and 250 nm	24 hours	77–120 μg/kg	Tail vein
Sonavane^Citation33	Naked	15, 50, 100, and 200 nm	24 hours	1000 μg/kg	Tail vein
Kim^Citation34	PBS buffered	20 and 100 nm	24 hours	1000 μg/kg	Tail vein
Chen^Citation35	Naked	3, 5, 8, 12, 17, 37, and 50 nm	21 days	8000 μg/g/week	Intraperitoneal
Cho^Citation36,Citation38	HS-PEG	4, 13, and 100 nm	4–30 min, 1–7 days	170–4200 μg/kg	Tail vein
Semmler-Behnke^Citation37	Naked	1.4 and 18 nm	24 h	54–530 μg/kg	Intratracheal and intravenous
Balasubramanian^Citation39	Naked	20 nm	1 day, 1 week, 1 and 2 months	10 μg/kg	Intravenous
Zhang^Citation41	PEG-TA or PEG-SH	20, 40, and 80 nm	48 h	100–4400 μg/kg	Tail vein
Lipka^Citation42	PEG	5 nm	1–24 h	570–870 μg/kg	Tail vein and intratracheal
Lasagna-Reeves^Citation47	Naked	12.5 nm	8 days	40–400 μg/kg/day	Intraperitoneal
Sadauskas^Citation50	Naked	40 nm	1 day, 1, 3, and 6 months	1400–1600 μg/kg	Tail vein
Fent^Citation53	Gum arabic- and maltose-coated	6–10 and 15–20 nm	1–24 hours and 7–32 days	2000 μg/kg	Intravenous
This work	Naked	13.5 nm	14, 28 days	137.5–2200 μg/kg	Tail vein, oral, intraperitoneal

Abbreviations: PEG, polyethylene glycol; PBS, phosphate-buffered saline.

Figure 4 Transmission electron microscopy figures for gold nanoparticles in bone marrow and blood cells 14 days after oral administration at 2200 μg/kg.

Figure 5 Thymus and spleen indices of mice after oral administration by different doses (137.5–2200 μg/kg) (A) after 14 days and the different injection routes at the dose of 1100 μg/kg (B) after 28 days.

Note: All values are reported as means ± standard deviation. Data were analyzed by Student’s t- test. *Represents significant difference from the control group (P < 0.05).

Abbreviations: ORAL, oral administration; INTER, intraperitoneal injection; TAIL, tail vein injection.

Table 2 Weight of organs for liver, lung, spleen, kidneys, brain, heart, and thymus after oral administration of different doses (137.5–2200 μg/kg) for 14 days

Dose (μg/kg)	Control	137.5	275	550	1100	2200
Heart (g)	0.194 ± 0.048	0.185 ± 0.037	0.167 ± 0.057	0.105 ± 0.017	0.104 ± 0.027	0.099 ± 0.031
Liver (g)	1.431 ± 0.036	1.437 ± 0.433	1.321 ± 0.452	1.206 ± 0.197	1.348 ± 0.074	1.071 ± 0.012
Spleen (g)	0.120 ± 0.004	0.126 ± 0.009	0.160 ± 0.068	0.109 ± 0.005	0.103 ± 0.047	0.095 ± 0.002
Lung (g)	0.305 ± 0.060	0.215 ± 0.035	0.246 ± 0.052	0.235 ± 0.019	0.140 ± 0.040	0.150 ± 0.015
Kidneys (g)	0.215 ± 0.048	0.200 ± 0.057	0.221 ± 0.054	0.135 ± 0.001	0.135 ± 0.011	0.122 ± 0.002
Thymus (g)	0.034 ± 0.002	0.067 ± 0.011	0.062 ± 0.008	0.054 ± 0.013	0.048 ± 0.003	0.056 ± 0.011
Brain (g)	0.391 ± 0.028	0.410 ± 0.003	0.389 ± 0.043	0.349 ± 0.009	0.370 ± 0.045	0.213 ± 0.006

Data were analyzed by Student’s t-test and the differences between the doses for each organ were not significant (P > 5% versus controls). All values represent the mean ± standard deviation for six mice.

Table 3 Weight of organs for liver, lung, spleen, kidneys, brain, heart, and thymus by using oral, intraperitoneal, and tail vein injection at doses of 1100 μg/kg at 28 days

Dose (μg/kg)	Control (Oral)	Oral administration	Control (Intraperitoneal)	Intraperitoneal injection	Control (Tail vein)	Tail vein injection
Heart (g)	0.195 ± 0.025	0.082 ± 0.011	0.237 ± 0.005	0.222 ± 0.005	0.202 ± 0.002	0.132 ± 0.058
Liver (g)	2.234 ± 0.339	1.329 ± 0.177	1.853 ± 0.086	1.832 ± 0.176	1.643 ± 0.099	1.157± 0.226
Spleen (g)	0.176 ± 0.042	0.342 ± 0.058	0.129 ± 0.042	0.123 ± 0.011	0.138 ± 0.036	0.061 ± 0.003
Lung (g)	0.278 ± 0.049	0.243 ± 0.057	0.521 ± 0.022	0.198 ± 0.024	0.209 ± 0.078	0.191 ± 0.012
Kidneys (g)	0.232 ± 0.044	0.162 ± 0.028	0.248 ± 0.038	0.237 ± 0.068	0.235 ± 0.036	0.182 ± 0.009
Thymus (g)	0.095 ± 0.020	0.060 ± 0.005	0.036 ± 0.006	0.068 ± 0.001	0.076 ± 0.008	0.022 ± 0.002
Brain (g)	0.411 ± 0.014	0.387 ± 0.013	0.437 ± 0.002	0.450 ± 0.043	0.412 ± 0.025	0.422 ± 0.003

Data were analyzed by Student’s t-test and the differences between the administration routes for each organ are not significant (P > 5% versus controls). All values represent the mean ± standard deviation for six mice.

Figure 6a Hematology results from mice treated with gold nanoparticles and the control group after 14 days oral administration by different doses (137.5–2200 μg/kg).

Note: Bars represent mean ± standard deviation. Data were analyzed by Student’s t-test.

*Represents significant difference from the control group (P < 0.05).

Abbreviations: PLT, platelets; HCT, hematocrit; HGB, hemoglobin; RBC, red blood cells; WBC, white blood cells.

Figure 6b Hematology results from mice treated with gold nanoparticles and control groups after 28 days oral administration, intraperitoneal injection, and tail vein injection at the dose of 1100 μg/kg.

Note: Bars represent mean ± standard deviation. Data were analyzed by Student’s t-test.

*Represents significant difference from the control group (P < 0.05).

Abbreviations: PLT, platelets; HCT, hematocrit; HGB, hemoglobin; RBC, red blood cells; WBC, white blood cells; O/C, oral administration control; I/C, intraperitoneal injection/control; T/C, tail vein injection/control.

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