Treating colon cancer with a suicide gene delivered by self-assembled cationic MPEG-PCL micelles
Treating colon cancer with a suicide gene delivered by self-assembled cationic MPEG-PCL micelles
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利用自组装阳离子 MPEG-PCL 胶束传递的自杀基因治疗结肠癌
DOI：
10.1039/c2nr30079f
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发表时间：
2012-01-01
期刊：
影响因子：
6.7
通讯作者：
Wei, YuQuan
中科院分区：
文献类型：
--
作者：
Duan, XingMei;Wang, Pan;Wei, YuQuan
可生物降解的阳离子胶束在基因传递中有着广阔的应用前景。本文利用DOTAP对单甲氧基聚乙二醇-聚己内酯（MPEG-PCL，MP）胶束进行一步修饰，制备了新型阳离子自组装DOTAP和MPEG-PCL杂化胶束（PEG-PCL，MP）。这些胶束的平均粒径为46 +/- 5.6 nm，zeta电位为41.8 +/- 0.5 mV，并具有结合DNA的能力。与金标准PEI 25 K相比，胶束具有更高的转染效率和更低的细胞毒性。此外，我们还使用了Survivin-T34 A基因（S-T34 A，一种自杀基因）来治疗结肠癌。Survivin/S-T34 A能诱导癌细胞凋亡，并能抑制C-26结肠癌细胞的生长。体内研究表明，腹膜内施用胶束递送Survivin-T34 A基因并有效地抑制腹部转移性C-26结肠癌和恶性腹水的生长。这些数据表明，大肠杆菌可能是一种新的基因载体，其S-T34 A基因的传递可能在结肠癌的治疗中有很好的应用前景。
Biodegradable cationic micelles show promise for applications in gene delivery. In this article, we used DOTAP to modify monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL, MP) micelles in one step, creating novel cationic self-assembled DOTAP and MPEG-PCL hybrid micelles (DMP). These micelles had a mean particle size of 46 +/- 5.6 nm and a zeta potential of 41.8 +/- 0.5 mV, and had the capacity to bind DNA. Compared with PEI25K (the gold standard), DMP micelles had higher transfection efficiency and lower cytotoxicity. Moreover, we used DMP to deliver the Survivin-T34A gene (S-T34A, a suicide gene) to treat colon cancer. DMP delivered the Survivin-T34A gene (DMP/S-T34A) and could induce apoptosis in cancer cells, resulting in inhibition of the growth of C-26 colon cancer cells in vitro. An in vivo study indicated that intraperitoneal administration of DMP micelles delivered the Survivin-T34A gene and efficiently inhibited the growth of abdominal metastatic C-26 colon cancer and the malignant ascites. These data suggest that DMP may be a novel gene carrier, and its delivery of the S-T34A gene may have promising applications in the treatment of colon cancer.