Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells

Table 1 Results of MTT test (mean  ±  SD)

Group	Absorbance value	RGR (%)	Cytotoxicity gradations
Negative control	0.4671 ± 0.0103	100.00	0
25% Fe2O3	0.4793 ± 0.0210	102.63	0
50% Fe2O3	0.4501 ± 0.0101	96.39	0
100% Fe2O3	0.4453 ± 0.0108	95.35	0
25% As2O3/Fe2O3	0.4373 ± 0.0210	93.64	0
50% As2O3/Fe2O3	0.1788 ± 0.0247	38.29	3
100% As2O3/Fe2O3	0.1273 ± 0.0073	27.26	3
As2O3 (5 &mgr;mol/L)	0.1322 ± 0.0090	30.12	3
Positive control	0.0733 ± 0.0050	15.70	4

Table 2 Results of hemolytic test of Fe₂O₃ and As₂O₃/Fe₂O₃ liquid extracts

Group	Absorbance (A)			Average A	Hemolysis rate (HR, %)
	1	2	3
Negative control	0.234	0.234	0.236	0.235
Fe2O3 extract	0.232	0.235	0.233	0.233	0.00
As2O3/Fe2O3 extract	0.246	0.246	0.246	0.246	0.77
Positive control	1.688	1.776	1.521	1.662

Table 3 Results of micronucleus assay (n = 10)

Groups	PEC	PEC containing MN	MN-formation rates (%), mean ± SD
Negative control	10 000	24	0.24 ± 1.58
Positive control	10 000	241	24.1 ± 4.63
Fe2O3	10 000	18a	0.28 ± 1.40
As2O3/Fe2O3	10 000	29a	0.26 ± 1.65

^aP < 0.05 compared with negative control group.

Table 4 Results of acute toxicity test of Fe₂O₃

Groups	Dose (g/kg)	Log	N	Deaths (N)	Mortality % (p)	Survival % (q)	p×q
1	10.00	1.000	10	10	100	0	0.00
2	7.07	0.849	10	4	40	60	0.24
3	5.00	0.699	10	4	40	60	0.24
4	3.50	0.544	10	2	20	80	0.16
5	2.50	0.398	10	0	0	100	0.00
6	1.75	0.243	10	1	10	90	0.09
7	1.25	0.097	10	0	0	100	0.00
	i = 0.15			∑p = 2.1

lgLD₅₀ = 1-0.15 (2.1-0.5) = 0.76, Sm = 0.04, Fe₂O₃ Lg LD₅₀ and its 95% CI: 0.76 ± 1.96 × 0.04 = 0.76 ± 0.079, Fe₂O₃ LD₅₀ and its 95% CI: 5.75 g/kg (4.80-6.90 g/kg).

Table 5 Results of acute toxicity test of As₂O₃/Fe₂O₃

Groups	Dose (g/kg)	Log	N	Deaths (N)	Mortality % (p)	Survival % (q)	p×q
1	10.00	1.000	10	10	100	0	0.00
2	7.07	0.849	10	5	50	50	0.25
3	5.00	0.699	10	3	30	70	0.21
4	3.50	0.544	10	3	30	70	0.21
5	2.50	0.398	10	1	10	90	0.09
6	1.75	0.243	10	0	0	100	0.00
	i = 0.15			∑p = 2.2

lgLD₅₀ = 1-0.15 (2.2-0.5) = 0.745, Sm = 0.0414, As₂O₃/Fe₂O₃ Lg LD₅₀ and its 95% CI: 0.745 ± 1.96 × 0.0414 = 0.745 ± 0.0811, As₂O₃/Fe₂O₃ LD₅₀ and its 95% CI: 5.56 g/kg (4.56-6.70 g/kg).

Table 6 Results of biocompatibility study in vivo (mean  ±  SD)

Groups	TB	ALT	AST	Bun	Cr
Control	4.8 ± 1.67	41.5 ± 10.08	92.25 ± 46.81	3.3 ± 0.36	86.5 ± 6.19
Fe2O3 low dose	8.025 ± 2.70	44.25 ± 16.35	87 ± 29.01	3 ± 0.99	83.25 ± 4.65
Fe2O3 high dose	6.45 ± 2.97	34.5 ± 9.61	71.25 ± 35.64	2.475 ± 0.46	77.5 ± 15.44
As2O3/Fe2O3	7.93 ± 2.66	47.25 ± 14.19	52.75 ± 5.5	2.5 ± 0.25	92.25 ± 19.69

Compared with control group: P > 0.05 .

Table 7 Volume and mass inhibitory rate of xenograft liver cancer in nude mice after treatment

Groups	Tumor mass (g, mean ± SD)	Mass inhibitory rate (%)	Tumor volume (cm3, mean ± SD)	Volume inhibitory rate (%)
Control	0.6145 ± 0.2296	0.00	0.7195 ± 0.3231	0.00
As2O3	0.5885 ± 0.1628	5.86	0.6015 ± 0.2282	16.40
Fe2O3	0.5365 ± 0.2792	12.69	0.5997 ± 0.2518	16.65
As2O3/Fe2O3	0.4548 ± 0.2591	26.04	0.6252 ± 0.4034	21.45
Fe2O3 with MFH	0.1921 ± 0.0395	68.74b	0.2373 ± 0.0874	67.02b
As2O3/Fe2O3 with MFH	0.1057 ± 0.0510	82.79bc	0.1183 ± 0.0726	83.56bc

^bP < 0.01 vs control group;

^cP < 0.05 vs Fe₂O₃ with MFH group.