siRNA nanoformulation against the ret/PTC1 junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma.
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.
de Martimprey
Henri
H
CNRS, UMR 8121, Univ Paris-Sud, Institut Gustave Roussy, Naples, Italy. martimprey@igr.fr
Bertrand
Jean-Remi
JR
Fusco
Alfredo
A
Santoro
Massimo
M
Couvreur
Patrick
P
Vauthier
Christine
C
Malvy
Claude
C
D000327:Adsorption; D000818:Animals; D002015:Bucrylate / Q000737:chemistry; D002291:Carcinoma, Papillary / Q000628:therapy*; D002461:Cell Line, Transformed; D048271:Chitosan / Q000737:chemistry; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry*; D015514:Oncogene Proteins, Fusion / Q000037:antagonists & inhibitors* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011108:Polymers / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D017423:Sequence Analysis, RNA; D013964:Thyroid Neoplasms / Q000628:therapy*
D015514:Oncogene Proteins, Fusion; D011108:Polymers; D034741:RNA, Small Interfering; D002015:Bucrylate; D048271:Chitosan; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human