siRNA nanoformulation against the Ret/PTC1 junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma

被引：58

作者：

de Martimprey, Henri ^{[1
,2
]}

Bertrand, Jean-Remi ^{[1
]}

Fusco, Alfredo ^{[3
]}

Santoro, Massimo ^{[3
]}

Couvreur, Patrick ^{[2
]}

Vauthier, Christine ^{[2
]}

Malvy, Claude ^{[1
]}

机构：

[1] Univ Paris Sud, CNRS, UMR 8121, Inst Gustave Roussy, Paris, France

[2] Univ Paris Sud, CNRS, UMR 8612, Fac Pharm, Paris, France

[3] Univ Naples Federico II, Ist Endocrinol & Oncol Sperimentale, CNR G Salvatore, Dipartimento Biol & Patol Cellulare & Mol, Naples, Italy

来源：

NUCLEIC ACIDS RESEARCH | 2008年 / 36卷 / 01期

基金：

澳大利亚研究理事会;

关键词：

D O I：

10.1093/nar/gkm1094

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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.

引用

页数：13

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