ABSTRACT
OBJECTIVE: To investigate the in vivo tissue distribution of hydroxyapatite nanoparticles (HANPs) and provide important information for the in vivo biosafety evaluation of HANPs. METHODS: The HANPs were modified with aminopropyltriethoxysilane (APTS) to introduce amino groups on the surface. The modified HANPs were labeled with 125I and injected into mice. A γ-counter was used to quantitatively assess the radioactivity of the tissues. The accumulation of HANPs in the tissues was expressed as the percentage injected dose per gram tissue (%ID · g-1). RESULTS: The HANPs mainly accumulated in the lung, liver, and spleen. One day post-injection, the accumulation in these tissues was over 5% ID · g-1. During 30 d after the injection, the accumulation of HANPs in the lung decreased quickly, while the accumulation in the liver and spleen reduced moderately and maintained at more than 2% ID · g-1. CONCLUSION: This study indicates that lung, liver and spleen are the main tissues for the in vivo biosafety evaluation of HANPs. KEY
ABSTRACT
Objective To study the inhibitory effects of hydroxyapatite nanoparticles on liver VX2 tumor in rabbits after intratumoral injection. Methods 40 rabbits with implantation of liver VX2 tumors were randomly divided into 4 groups and intratumorally injected with different preparations.Group A: (control group), 1 ml nomal saline containing 0.2% CMC-Na; Group B: ( 5-Fu group),20 mg/ml 5-Fu 1 ml; Group C: (Nano HAP), 20 mg/ml Nano HAP 1 ml; Group D: (5-Fu+Nano HAP), 20 mg/ml 5-Fu 1 ml and 20 mg/ml Nano HAP 1 ml. Ultrasonography was performed to measure liver tumor volume 7, 14, 21 d after treatment. Survival durations of the animals were recorded. Tumor tissues and liver tissues close to tumor were obtained and examined histologically.Results The average tumor volumes 7, 14 and 21 d after treatment were (4.93 ±0.76)cm3,(15. 67±2.75)cm3 and (52. 36±10. 57)cm3 in group A, (4. 16±0. 33)cm3 , (10. 26± 1.60)cm3 and (18. 89±4.65)cm3 in group B, (1.43±0.13)cm3 , (3.69±0.77)cm3 and (9.51±2.09)cm3 in group C, (2. 80±0.46)cm3 , (3. 77±0. 91)cm3 and (8. 46±0.95)cm3 in group D respectively. The average tumor volumes of groups B, C and D were significantly smaller than that of group A in the same time phases after treatment. The life span of group C was longer than that of other three groups, and there was no statistically significant difference between group B and group D, although the two groups were significantly longer than group A. Blood flow was not detected by color Doppler or power Doppler in group C and group D. Pathological examination showed that there was obvious intratumoral necrosis in group C and D. Tumor in group B exhibited thoroughgoing necrosis. Conclusion Hydroxyapatite nanoparticles intratumoral injection is safe and feasible for treatment of liver tumor. Hydroxyapatite nanoparticles can exert a significant inhibitory effect on liver VX2 tumor growth in rabbits without liver toxicity.
ABSTRACT
Objective To study expression of CD147 in rabbit VX2 tumor tissues after transarterial embolization with hydroxyapatite nanoparticles loaded with lipiodol.Methods Thirty rabbits implanted with tumor tissue of cell line VX2 were divided into three groups: control group, lipiodol group, and hydroxyapatite nanoparticles loaded with lipiodol group. The transarterial embolization was performed superselectively via gastroduodenal artery of rabbits, and each rabbit in control group was infused with 1ml normal saline, that in lipiodol group was infused with 0.3ml lipiodol per kg, and o.3ml hydroxyapatite nanoparticles loaded with lipiodol per kg for that in the last group.Results of treatment were detected by using CT on day 3 after operation. After two weeks, three-step Immunohistochemical technique(S-P) and Western blot technique were used to investigate the expression of CD147 in tumor tissues of the 3 groaps. Results Immunohistochemical results showed that CD147 was expressed on membrane of tumor cells in all three groups. The positive ratios of CD147 in three groups were (31.33?5.88)%,(75.63?4.44)%, and (80.03?5.59)% respectively, while the expression of CD147 in tumor tissues in control group was significantly different from others(P0.05). Protein half-quantitation detecting of CD147 with Western blot technique displayed that expression of CD147 in tumor tissues increased after embolization in last two groups as compared to that of control group(P