槲皮素PLGA-TPGS纳米粒在荷HCa-F细胞小鼠体内肝靶向性的研究

Investigation of the Liver-targeting Properties of Quercetin-loaded PLGA-TPGS Nanoparticles in HCa-F Cell-bearing Mice

目的评价槲皮素(QT)/香豆素6(C6)乳酸羟基乙酸共聚物-水溶性维生素E纳米粒(QCPTN)在荷肝癌细胞HCa-F异位实体瘤小鼠体内的分布及对小鼠肝脏的靶向性。方法建立RP-HPLC法测定QT在荷肝癌细胞HCa-F异位实体瘤小鼠血浆及肝、实体瘤、脾、肺、肾和心的浓度。将QCPTN和QT溶液(QTS)经小鼠尾静脉注射后,测定不同给药时间后小鼠血浆及各组织中的QT浓度。采用相对靶向效率(Re)和靶向效率(Te),同时通过对各组织进行冰冻切片、荧光倒置显微镜下观察荧光纳米粒QCPTN在各组织的分布,定性、定量地全面评价QCPTN对肝脏的靶向性。结果 QCPTN在血浆、实体瘤、脾、肺、肾、心中的Te均>3,表明QT在肝脏比血浆和其他组织匀浆中的曲线下面积(AUC)高3倍以上。冰冻切片图可见在1 h的QCPTN组小鼠各组织中,肝中荧光分布面积最大。结论 QCPTN对荷肝癌细胞HCa-F异位实体瘤小鼠肝脏有良好的靶向作用。

Objective The aim of this study was to investigate the distribution and liver-targeting properties of quereetin （QT）/coumarin 6 （C6） - loaded polylactic-co-glycolic acid-D-α-tocopherol polyethylene glycol 1000 succinate （PLGA-TPGS） nanoparticles （QCPTN） in a hepatocarcinoma ectopic transplantation solid tumor model using HCa-F cell-bearing mice. Methods The QT concentrations in biological samples were determined using reverse phase-high performance liquid clromatography （RP-HPLC） analysis. After intravenous administration to mice in the QCPTN and QTS groups, the QT concentration in plasma and in different tissues was simultaneously analyzed at the different time points. Detection indexes （relative targeting efficiency, Re; targeting efficiency, Te） and fluorescence inversion microscopy images of the frozen tissue （liver, solid tumor, spleen, lungs, kidneys, and heart） slices were used for quantitatively and qualitatively evaluating the liver-targeting properties of QCPTN in solid tmnor-bearing mice. Results Te of the QCPTN group in the plasma, liver, solid tumor, spleen, lungs, kidneys, and heart were all greater than 3, indicating that the area under the concentration-time curve （AUC） of liver was more than three times that of the plasma and other organs. Fluorescence inversion microscopy images showed that the green fluorescence of QCPTN was mostly observed in the liver. Conclusion Using HCa-F cell- bearing mice, QCPTN was found to have better in vivo liver-targeting properties in hepatoeareinoma ectopic transplantation solid tumor.