文章：

细胞外囊泡介导的自杀mRNA/蛋白递送抑制胶质母细胞瘤肿瘤的体内生长

Extracellular vesicle-mediated suicide mRNA/protein delivery inhibits glioblastoma tumor growth in vivo 

原文发布日期：2016-12-16 

英文摘要：

Extracellular vesicles (EVs) are considered as important mediators of intercellular communication, which carry a diverse repertoire of genetic information between cells. This feature of EVs can be used and improved to advance their therapeutic potential. We have previously shown that genetically engineered EVs carrying the suicide gene mRNA and protein—cytosine deaminase (CD) fused to uracil phosphoribosyltransferase (UPRT)—inhibited schwannoma tumor growth in vivo. To further examine whether this approach can be applied to other cancer types, we established a subcutaneous xenograft glioblastoma tumor model in mice, as glioblastoma represents the most common primary brain tumor, which is highly aggressive compared with the original schwannoma tumor model. U87-MG glioblastoma cells were implanted into the flanks of nude SCID mice, and the animals were intratumorally injected with the EVs isolated from the cells expressing EGFP or CD-UPRT. After the intraperitoneal administration of the prodrug 5-fluorocytosine, the tumor growth was assessed by regular caliper measurements. Our data revealed that the treatment with the CD-UPRT-enriched EVs significantly reduced the tumor growth in mice. Taken together, our findings suggest that EVs uploaded with therapeutic CD-UPRT mRNA/protein may be a useful tool for glioblastoma treatment. 

摘要翻译： 

细胞外囊泡（EVs）被视为细胞间通讯的重要介质，能在细胞间传递多样化的遗传信息。基于这一特性，我们可以通过优化改造进一步提升其治疗潜力。我们既往研究表明，携带自杀基因mRNA及胞嘧啶脱氨酶（CD）与尿苷磷酸核糖基转移酶（UPRT）融合蛋白的基因工程化EVs，能在体内抑制神经鞘瘤的生长。为验证该方法是否适用于其他癌症类型，我们建立了小鼠皮下异种移植胶质母细胞瘤模型——该肿瘤作为最常见的原发性脑肿瘤，相较于原始神经鞘瘤模型具有更高侵袭性。将U87-MG胶质母细胞瘤细胞植入裸鼠SCID小鼠侧腹后，对荷瘤小鼠瘤内注射从表达EGFP或CD-UPRT的细胞中分离的EVs。在腹腔注射前药5-氟胞嘧啶后，通过定期卡尺测量评估肿瘤生长。数据显示，经CD-UPRT富集型EVs治疗的小鼠肿瘤生长显著减缓。综上所述，我们的研究结果表明，装载治疗性CD-UPRT mRNA/蛋白的EVs可能成为胶质母细胞瘤治疗的有效工具。

原文链接：

Extracellular vesicle-mediated suicide mRNA/protein delivery inhibits glioblastoma tumor growth in vivo