State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
Nanoscale. 2012 Apr 7;4(7):2400-7. doi: 10.1039/c2nr30079f. Epub 2012 Mar 2.
Biodegradable cationic micelles show promise for applications in gene delivery. In this article, we used DOTAP to modify monomethoxy poly(ethylene glycol)-poly(ε-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.
可生物降解的阳离子胶束在基因传递应用中具有广阔的前景。在本文中，我们采用 DOTAP 一步法对单甲氧基聚乙二醇-聚（ε-己内酯）（MPEG-PCL，MP）胶束进行修饰，制备了新型阳离子自组装 DOTAP 和 MPEG-PCL 杂化胶束（DMP）。该胶束平均粒径为 46±5.6nm，Zeta 电位为 41.8±0.5mV，具有结合 DNA 的能力。与 PEI25K（金标准）相比，DMP 胶束具有更高的转染效率和更低的细胞毒性。此外，我们采用 DMP 递送 Survivin-T34A 基因（S-T34A，自杀基因）用于治疗结肠癌。DMP 递送 Survivin-T34A 基因（DMP/S-T34A）可诱导癌细胞凋亡，从而抑制体外 C-26 结肠癌细胞的生长。体内研究表明，腹腔内给予 DMP 胶束递送 Survivin-T34A 基因可有效抑制腹部转移性 C-26 结肠癌和恶性腹水的生长。这些数据表明，DMP 可能是一种新型的基因载体，其递送 S-T34A 基因可能在结肠癌的治疗中有很好的应用前景。
