超声波纳米粒子介导的胎盘干细胞自杀基因转染
Suicide-Gene Transfection of Tumor-tropic Placental Stem Cells employing Ultrasound-Responsive Nanoparticles
摘要：
本文提出了一种采用非病毒纳米载体转染的肿瘤嗜性间充质干细胞进行癌症治疗的特洛伊木马策略。从这个意义上说，超声响应介孔二氧化硅纳米粒子被聚阳离子（使用两种不同的分子量）包覆，为它们提供了基因转染能力，使用两种不同的质粒进行了评估。首先，在与二氧化硅纳米颗粒孵育后，分析了蜕膜来源的间充质干细胞中绿色荧光蛋白的表达。最成功的纳米颗粒被用来诱导两种自杀基因的表达：胞嘧啶脱氨酶和尿嘧啶磷酸核糖转移酶，这使得细胞将无毒的前药（5-氟胞嘧啶）转化为有毒的药物（5-氟尿苷一磷酸）。还在与转染的载体细胞（蜕膜衍生的间充质干细胞）共培养的癌细胞系（NMU细胞）中评价了毒性终产物产生的影响。
英文摘要：
A Trojan-horse strategy for cancer therapy employing tumor-tropic mesenchymal stem cells transfected with a non-viral nanovector is here presented. In this sense, ultrasound-responsive mesoporous silica nanoparticles were coated with a polycation (using two different molecular weights), providing them with gene transfection capabilities that were evaluated using two different plasmids. First, the expression of Green Fluorescent Protein was analyzed in Decidua-derived Mesenchymal Stem Cells after incubation with the silica nanoparticles. The most successful nanoparticle was then employed to induce the expression of two suicide genes: cytosine deaminase and uracil phosphoribosyl transferase, which allow the cells to convert a non-toxic pro-drug (5-fluorocytosine) into a toxic drug (5-Fluorouridine monophosphate). The effect of the production of the toxic final product was also evaluated in a cancer cell line (NMU cells) co-cultured with the transfected vehicle cells, Decidua-derived Mesenchymal Stem Cells.
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