转铁蛋白受体单克隆抗体修饰纳米粒给药系统治疗白血病的基础研究
[Basic Research on Therapy of Leukemia with Nanoparticles Drug Delivery System Modified by Transferrin Receptor Monoclonal Antibody].
作者信息
Bao Wen, Liu Ran, Wang Fei, Nie Chao, Qian Li-Bing, Chen Ling, Wang Yan, Chen Bao-An
机构信息
Jiangsu Health Vocational College， Nangjing 211800， Jiangsu Province， China.
Department of Hematology， Zhongda Hospital， Southeast University Medical College， Nangjing 210009， Jiangsu Province， China.
出版信息
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023;31(4):939-944. doi: 10.19746/j.cnki.issn.1009-2137.2023.04.002.
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（<0.05）. The apoptotic rate of HL60 cells in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that of DNR group（<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（<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.
目的
探讨转铁蛋白受体单克隆抗体（TfR mAb）修饰的靶向载药纳米粒对急性白血病的治疗效果及其潜在的抗肿瘤机制。
方法
首先合成由聚乳酸-羟基乙酸共聚物、聚-L-赖氨酸、聚乙二醇、TfR mAb（TfR mAb-PLGA-PLL-PEG）-柔红霉素（DNR）组成的纳米粒给药系统。药物干预后，在荧光显微镜下观察白血病HL60细胞内的蓄积情况，并用流式细胞术（FCM）测定DNR浓度。同时，用FCM检测细胞凋亡率，并用蛋白质免疫印迹法检测凋亡相关蛋白Cleaved-caspase 3的表达水平。
结果
在倒置荧光显微镜下，TfR mAb-PLGA-PLL-PEG-DNR组和DNR组HL60细胞内均观察到DNR自发荧光的蓄积。FCM分析显示，TfR mAb-PLGA-PLL-PEG-DNR组细胞内DNR浓度高于DNR组（<0.05）。TfR mAb-PLGA-PLL-PEG-DNR组HL60细胞凋亡率高于DNR组（<0.05）。此外，TfR mAb-PLGA-PLL-PEG-DNR组凋亡相关蛋白Cleaved-caspase 3的表达水平明显高于DNR组（<0.05）。
结论
TfR mAb-PLGA-PLL-PEG纳米粒给药系统可将化疗药物靶向白血病细胞，并通过凋亡途径增强抗癌能力。
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