iRGD修饰的外泌体携载阿霉素对U87MG胶质瘤细胞的疗效研究  

Study on the efficacy of iRGD-modified doxorubicin-loaded exosomes for U87MG glioma cells

作　　者：孙雷涛[1] 刘立云[1] 张文生[1] SUN Leitao;LIU Liyun;ZHANG Wensheng(Department of Neurosurgery,Binzhou Medical University Hospital,Shandong,Binzhou 256600,China)

机构地区：[1]滨州医学院附属医院神经外科,山东滨州256600

出　　处：《中国医药科学》2022年第21期24-27,51,共5页China Medicine And Pharmacy

基　　金：山东省医药卫生科技发展计划项目(2018WS550)。

摘　　要：目的探讨iRGD修饰的外泌体携载阿霉素对胶质瘤细胞系U87MG的靶向性及体外增殖的有效性。方法构建胶质瘤细胞靶向载体并体外转染U87MG细胞,设置为空白转染组和iRGD靶向转染组,通过电穿孔包裹阿霉素后分为空白转染-外泌体-阿霉素组与iRGD-外泌体-阿霉素组,分别与U87MG细胞共孵育,通过激光共聚焦比较细胞对两组外泌体的摄取情况及阿霉素的胞内浓度,并通过CCK-8增殖实验检测iRGD靶向修饰的外泌体携载阿霉素后对U87MG细胞增殖的影响。结果成功构建了携载阿霉素并靶向U87MG细胞的外泌体载体iRGD-外泌体-阿霉素,发现该载体与U87MG细胞的结合率为(45.60±9.15)%,显著高于空白转染-外泌体-阿霉素组的(9.20±3.46)%,差异有统计学意义(P<0.05),且高效靶向U87MG细胞后增加了胞内阿霉素浓度,显著抑制了细胞增殖,24、48、72 h细胞增殖抑制率分别为(52.33±8.94)%、(70.15±6.20)%和(87.16±13.01)%,均显著高于空白转染-外泌体-阿霉素组,差异有统计学意义(P<0.05)。结论iRGD-外泌体-阿霉素通过靶向作用于U87MG胶质瘤细胞,增加了胞内阿霉素浓度进而能够高效抑制胶质瘤细胞的增殖。Objective To investigate the targeting effect and the effectiveness of proliferation in vitro of U87MG glioma cell line by iRGD-modified doxorubicin-loaded exosomes.Methods Glioma cell targeting vector was constructed and transfected into U87MG cells in vitro.The cells were set as the blank transfection group and the iRGD targeted transfection group.Doxorubicin was encapsulated by electroporation,the two groups were further divided into the blank transfection-exosomes-doxorubicin group and iRGD-exosomes-doxorubicin group.They were incubated with U87MG cells respectively.The cellular uptake of exosomes and the intracellular concentration of doxorubicin in the two groups were compared by laser confocal microscopy,and the effect of iRGD targeted modified doxorubicinloaded exosomes on the proliferation of U87MG cells was detected by CCK-8 proliferation assay.Results The iRGD-exosomes-doxorubicin vector loaded with doxorubicin and targeting U87MG cells was successfully constructed.It was found that the binding rate of the iRGD-exosomes-doxorubicin vector to U87MG cells(45.60±9.15)%was significantly higher than that in the blank transfectionexosomes-doxorubicin group(9.20±3.46)%,and the difference was statistically significant(P<0.05).After effectively targeting U87MG cells,the intracellular concentration of doxorubicin was increased and cell proliferation was significantly inhibited.The cell growth inhibition rates at 24,48 and 72 hours were(52.33±8.94)%,(70.15±6.20)%and(87.16±13.01)%,respectively,which were significantly higher than those in the blank transfection-exosomes-doxorubicin group,and the differences were statistically significant(P<0.05).Conclusion iRGD-exosomes-doxorubicin can effectively inhibit the proliferation of glioma cells by targeting U87MG glioma cells and increasing the intracellular concentration of doxorubicin.

关 键 词：外泌体 胶质瘤 靶向修饰 阿霉素 

分 类 号：R739.41[医药卫生—肿瘤]