ABSTRACT
Objective To preliminarily explore the anti?cancer efficiency of disulfide?bonded hyaluronic acid?functionalized targeted sodium?meter probe for hepatocellular carcinoma and the feasibility of MRI. Methods Twenty?one nude mice models of subcutaneous liver cancer transplantation were randomly divided into saline, hyaluronic acid?poly ε?caprolactone@ doxorubicin/superparamagnetic iron oxide (HA?PCL@DOX/SPIO) and HA?disulfide?bonded?PCL@DOX/SPIO (HA?SS?PCL@DOX/SPIO) groups, with 7 mice in each group. The experimental groups were injected with micelles at a dose of Fe 5 mg/kg through the tail vein, and the control group was injected with the same amount of saline via the tail vein. MRI was performed before and after injection (2 h, 4 h, 8 h). The T2 value of the region of interest (tumor) was measured and its decline rate was calculated. Twenty?one nude mice models of orthotopic liver cancer transplantation were randomly divided into saline group,HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups, with 7 mice in each group. The experimental groups were injected with micelles at a dose of DOX 2 mg/kg through the tail vein by three consecutive times a day apart, and the control group was injected with the same amount of saline through the tail vein. Continuous observation for 15 days to calculate tumor inhibition rate. One way ANOVA test was used. Results The T2 value of HA?SS?PCL@DOX/SPIO group decreased significantly after 2, 4 and 8 hours (P<0.05) than initial time, which was distinct compared with HA?PCL@DOX/SPIO group. The growth rate of tumor in HA?SS?PCL@DOX/SPIO and HA?PCL@DOX/SPIO groups was significantly lower than that in the control group (F=21.513,P<0.05). The former had the most obvious inhibitory effect on orthotopic liver cancer (47.7% and 28.2%). Conclusion Disulfide?bonded hyaluronic acid?functionalized targeted sodium?meter probe for hepatocellular carcinoma(HA?SS?PCL@DOX/SPIO) has high anti?cancer efficiency and imaging function at the animal level in vivo, and can be used to monitor the early therapeutic effect of tumor at the molecular imaging level.
ABSTRACT
Objective To explore the construction method and physicochemical properties of disulfide?bonded hyaluronic acid?functionalized sodium?meter probe for hepatocellular carcinoma, and its biological evaluation in vitro and feasibility of MRI. Methods Synthesis of hyaluronic acid?disulfide?bonded?poly ε?caprolactone (HA?SS?PCL) by disulfide?bonded alkynyl?terminated polycaprolacton (alkyne?SS?PCL) and azido?terminated hyaluronic acid (HA?N3) by clicking chemical reaction, then doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) were encapsulated in HA?SS?PCL core by dialysis method.HA?SS?PCL@DOX/SPIO was prepared and its particle size,DOX and SPIO loading rate were measured. With PBS as control group, the safety of HA?SS?PCL on human hepatocellular carcinoma cells HepG2 and normal liver cells LO2 was evaluated by the methylthiazolyl tetrazolium (MTT) assay, and the cytotoxicity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO on human hepatocellular carcinoma cells HepG2 was evaluated. Immunofluorescence and flow cytometry were used to observe the expression of CD44 receptor on the surface of HepG2 cells in HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups. Through in vitro MRI, PBS was used as the control group to observe the changes of T2 signal intensity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups when SPIO concentration was 10, 20, 40, 80 μg / ml. One way ANOVA test and t test were used. Results HA?SS?PCL@DOX / SPIO sodium?meter probes were successfully constructed. The particle size of HA?SS?PCL@DOX/SPIO was (126.9±6.3) nm,and they were spherical with uniform size. The loading rates of DOX and SPIO were 61.4% and 58.7%. MTT assay showed that the survival rate of HepG2 and LO2 cells was more than 80% even at 500 μg/ml of HA?SS?PCL, 66.6% in HA?PCL@DOX/SPIO group and 55.2% in HA?SS?PCL@DOX/SPIO group. Immunofluorescence and flow cytometry showed that HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO groups all have strong fluorescence, and the latter has stronger fluorescence intensity the former fluorescence intensity was 139.70±8.52,less than the latter 245.06±13.21. In vitro MRI showed that the T2 signal intensity of HA?PCL@DOX/SPIO and HA?SS?PCL@DOX/SPIO was significantly lower than that of the control group (F values were 613.591 and 569.234,P=0.000), the latter decline rate was more significant. Conclusion The disulfide?bonded hyaluronic acid?functionalized sodium?meter probe for hepatocellular carcinoma has excellent physicochemical properties, good targeting and MRI functions on human hepatoma cell HepG2 at the cellular level in vitro.
ABSTRACT
Objective To detect radiation-induced changes of temporal lobe normal-appearing white matter on conventional MRI following radiation therapy (RT) for nasopharyngeal carcinoma (NPC).Methods The clinical and imaging features of 75 patients with nasopharyngeal carcinoma were retrospectively analyzed,all patients were confirmed by biopsy.All patients performed conventional MRI and Diffusion-tensor imaging (DTI) examinations,and there was no abnormal finding on conventional MRI.Eighteen patients without radiotherapy were selected as the control group and fifty-seven patients with radiotherapy were as the experimental group.We divided the experimental group into five subgroups based on completion time of RT:group 1 (less than 3 months,n =16),group 2 (3 to 6 months,n =12),group 3 (6 to 9 months; n =10),group 4 (9 to12 months,n =8),and group 5 ( more than 12 months,n =11 ).The mean diffusivity ( MD),apparent diffusion coefficient ( ADC ),fractional anisotropy ( FA),radial diffusivity ( λ⊥ ) and axial diffusivity ( k ‖ ) were calculated in bilateral temporal lobe.One-way analysis of variance (one-way ANOVA) test was used for comparison among groups.Results The mean λ⊥ values of the control group and experimental groups ( group1-5 ) after radiotherapy were ( 6.075 ± 0.341 ) × 10 -4 (6.700±0.379) × 10-4,(6.976 ±0.527) ×10-4,(6.621 ±0.388) ×10-4,(6.751 ±0.460) ×10-4,(6.222 ±0.256) × 10-4 mm2/s,respectively.The mean λ ‖ values of the control group and experimental groups were (12.524±0.713) ×10-4,(11.764 ±0.574) ×l0-4,(11.842±0.471) ×10-4,(11.569 ± 0.552) × 10-4,( 12.050 ±0.614) × 10-4,( 12.100 ±0.529) × 10-4 mm2/s,respectively.The mean FA values of the control group and experimental groups were 0.452 ± 0.030,0.379 ± 0.028,0.382 ± 0.028,0.389 ± 0.032,0.388 ± 0.022,0.423 ± 0.232,respectively.The three indicators were significantly different among groups ( F =10.485,4.625,16.539,respectively,P ＜ 0.05 ). Multiple comparisons showed that λ⊥ increased significantly in group 1-4 compared with that in the control group.In group 5,λ ⊥ was not significantly different from that in the control group,λ ‖ decreased in group 1-3 compared with that in the control group,but was not significantly different in the control group and group 4-5. In all experimental groups,FA decreased significantly. MD and ADC values in experimental groups were not significantly different from those in the control group. Conclusion Diffusion tensor imaging is a noninvasive and quantitative method to detect the structural changes in WM after RT and can provide scientific evidence for the early diagnosis and intervention treatment of radiation-induced changes.