Objective: To investigate the therapeutic effect of targeted drug-loaded nanoparticles modified by transferrin receptor monoclonal antibody (TfR mAb) on acute leukemia and its potential anti-tumor mechanism.
Methods: Nanoparticles drug delivery system, which was composed of poly (lactic-co-glycolic acid), poly-l-lysine, polyethylene glycol, TfR mAb (TfR mAb-PLGA-PLL-PEG)-daunorubicin (DNR), was first synthesized. After drug intervention, the intracellular accumulation in leukemia HL60 cells was observed under a fluorescent microscope and concentration of DNR was determined by flow cytometry (FCM). Meanwhile, cell apoptosis rate was measured by FCM and the expression levels of apoptosis related protein Cleaved-caspase 3 was determined by Western blot.
Results: Under an inverted fluorescent microscope, intracellular accumulation of DNR autofluorescence in HL60 cells was observed in both TfR mAb-PLGA-PLL-PEG-DNR group and DNR group. FCM analysis showed that the intracellular concentration of DNR in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that in DNR group（P<0.05）. The apoptotic rate of HL60 cells in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that of DNR group（P<0.05）. Moreover, the expression levels of apoptosis-related protein Cleaved-caspase 3 in TfR mAb-PLGA-PLL-PEG-DNR group was significantly higher than that in DNR group（P<0.05）.
Conclusion: TfR mAb-PLGA-PLL-PEG nanoparticle drug delivery system can target chemotherapy drugs to leukemia cells and enhance anticancer ability through apoptotic pathway.
题目: 转铁蛋白受体单克隆抗体纳米载药系统 治疗白血病的基础研究.
目的: 探讨转铁蛋白受体单克隆抗体（TfR mAb）纳米载药系统靶向治疗急性白血病的效果及其潜在的抗肿瘤机制.
方法: 合成纳米载药粒TfR mAb-聚乳酸-羟基乙酸（PLGA）-聚L-赖氨酸（PLL）-聚乙二醇(PEG)- 柔红霉素（DNR）。急性髓性白血病细胞株HL60细胞经药物干预后，倒置荧光显微镜下观察细胞内DNR的累积；流式细胞技术（FCM）检测HL60细胞内DNR浓度及细胞凋亡率；Western blot测定凋亡相关蛋白Cleaved-caspase 3的表达量.
结果: 单药DNR组和TfR mAb-PLGA-PLL-PEG-DNR组HL60细胞内可见DNR自发荧光累积，且TfR mAb-PLGA-PLL-PEG-DNR组细胞内DNR浓度高于单药DNR组（P<0.05）；FCM检测结果显示，TfR mAb-PLGA-PLL-PEG-DNR组细胞凋亡率高于单药DNR组（P<0.05）；Western blot检测结果证实，TfR mAb-PLGA-PLL-PEG-DNR组凋亡相关蛋白Cleaved-caspase 3表达量明显高于单药DNR组（P<0.05）.
结论: TfR mAb-PLGA-PLL-PEG纳米载药系统将化疗药物靶向作用于肿瘤细胞HL60，可通过凋亡途径增加药物的抗肿瘤能力.
Keywords: apoptosis; nanoparticle; targeted drug delivery system; transferrin receptor monoclonal antibody.