| 负载化疗药物的外泌体对肝癌的靶向治疗研究 |
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| 引用本文： | 张杨,游阿彬,齐寒,张缘,左冰峰,尹海芳. 负载化疗药物的外泌体对肝癌的靶向治疗研究[J]. 天津医科大学学报, 2021, 0(3): 229-233 |
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| 作者姓名： | 张杨 游阿彬 齐寒 张缘 左冰峰 尹海芳 |
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| 作者单位： | 天津医科大学基础医学院细胞生物学系，天津 300070 |
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| 摘 要： | 目的:在小鼠肝癌皮下瘤模型中探究肝癌靶向肽介导负载甲氨蝶呤(MTX)的肝癌细胞来源外泌体(tumor-derived exosome-TEX)的抗肿瘤效果及不良反应.方法:利用超速离心法收集负载MTX的小鼠肝癌细胞来源的外泌体(TEXMTX);利用外泌体特异锚定短肽CP05将肝癌靶向肽SP94修饰在TEXMTX表面,活...
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| 关 键 词： | 肝细胞癌 外泌体 化疗药物 靶向治疗 |
Tumor-derived exosomes mediate targeted therapy in hepatocellular carcinoma mice |
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| ZHANG Yang,YOU A-bin,QI Han,ZHANG Yuan,ZUO Bing-feng,YIN Hai-fang. Tumor-derived exosomes mediate targeted therapy in hepatocellular carcinoma mice[J]. Journal of Tianjin Medical University, 2021, 0(3): 229-233 |
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| Authors: | ZHANG Yang YOU A-bin QI Han ZHANG Yuan ZUO Bing-feng YIN Hai-fang |
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| Affiliation: | Department of Cell Biology，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China |
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| Abstract: | Objective: To investigate the anti-tumor and adverse reactions of hepatocellular carcinoma（HCC）-targeting peptide modified tumor-derived exosomes（TEX） loaded with methotrexate（MTX） cargoes in a mouse model of subcutaneous HCC. Methods: Tumor-derived exosomes（TEXMTX） loaded with methotrexate was collected by ultracentrifugation. HCC-targeting peptides SP94 were modified on TEXMTX by using exosomal-specific anchoring peptide CP05. In vivo imaging was used to detect whether targeting peptide-modified TEXMTX could efficiently target HCC tissues. The tumor-bearing mice were injected through the tail vein to compare the anti-tumor effects of TEXMTX in each group. At the same time， the blood biochemical indexes and histomorphological staining of each group after treatment were detected to assess the biological safety of the drug. Results: Loading MTX did not affect the basic structure and morphological characteristics of exosomes. TEXMTX modified with SP94 improved the delivery efficiency of chemotherapy drugs into targeted HCC tumor tissue. In the subcutaneous tumor suppression experiment， compared with the PBS group， SP94-CP05-TEXMTX could significantly inhibit the growth of liver cancer subcutaneous tumors in mice（t=5.811，P＜0.01）. Compared with the MTX group and the TEXMTX group， the tumor volume in the SP94-CP05-TEXMTX group was also significantly reduced（t=2.573，3.152， both P＜0.05）. Blood biochemical indicators and pathological indicators showed that compared with the PBS group， the serum aspartate aminotransferase levels of mice in the MTX group and TEXMTX group were significantly increased（t=7.084， 5.260， both P＜0.05）. Compared with the MTX group and the TEXMTX group， the level of aspartate aminotransferase in mice of the SP94-CP05-TEXMTX group decreased significantly（t=6.241，4.955，both P＜0.05）. Compared with the MTX group， the SP94-CP05-TEXMTX group also showed a significant decrease in serum creatine kinase levels（t=5.073，P＜0.05）. Conclusion: HCC-targeting peptide modified TEXMTX can target MTX to hepatocellular carcinoma tissues， effectively inhibit the tumor growth， and improve the biological safety of chemotherapy drugs. |
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| Keywords: | hepatocellular carcinoma exosomes chemotherapeutics targeted therapy |
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