de Martimprey Henri, Bertrand Jean-Remi, Fusco Alfredo, Santoro Massimo, Couvreur Patrick, Vauthier Christine, Malvy Claude
CNRS, UMR 8121, Univ Paris-Sud, Institut Gustave Roussy, Naples, Italy.
Nucleic Acids Res. 2008 Jan;36(1):e2. doi: 10.1093/nar/gkm1094. Epub 2007 Dec 13.
Delivery is a very important concern for therapeutic applications of siRNA. In this study, we have used chitosan-coated poly(isobutylcyanoacrylate) nanoparticles to deliver siRNA with a complementary sequence to the fusion oncogene ret/PTC1. By screening the mRNA junction we have selected a potent siRNA sequence able to inhibit this oncogene in a model of Papillary Thyroid Carcinoma cells. This siRNA sequence has then been validated by a shRNA approach using the same sequence. Furthermore, the high ret/PTC1 inhibition has triggered a phenotypic reversion of the transformed cells. We have designed well-defined chitosan decorated nanoparticles and succeeded to reduce their size. They have allowed to protect ret/PTC1 siRNA from in vivo degradation and leading to significant tumour growth inhibition after intratumoral administration.
递送是小干扰RNA（siRNA）治疗应用中一个非常重要的问题。在本研究中，我们使用了壳聚糖包被的聚（异丁基氰基丙烯酸酯）纳米颗粒来递送与融合致癌基因ret/PTC1具有互补序列的siRNA。通过筛选mRNA连接处，我们在甲状腺乳头状癌细胞模型中选择了一个能够抑制该致癌基因的有效siRNA序列。然后，通过使用相同序列的短发夹RNA（shRNA）方法对该siRNA序列进行了验证。此外，对ret/PTC1的高度抑制引发了转化细胞的表型逆转。我们设计了明确的壳聚糖修饰纳米颗粒，并成功减小了它们的尺寸。这些纳米颗粒能够保护ret/PTC1 siRNA在体内不被降解，并在瘤内给药后导致显著的肿瘤生长抑制。
