Impact of the structure of biocompatible aliphatic polycarbonates on siRNA transfection ability.
Fiche publication
Date publication
mars 2015
Journal
Biomacromolecules
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PEIXOTO Paul
Tous les auteurs :
Frère A, Kawalec M, Tempelaar S, Peixoto P, Hendrick E, Peulen O, Evrard B, Dubois P, Mespouille L, Mottet D, Piel G
Lien Pubmed
Résumé
RNAi therapeutics are promising therapeutic tools that have sparked the interest of many researchers. In an effort to provide a safe alternative to PEI, we have designed a series of new guanidinium- and morpholino-functionalized biocompatible and biodegradable polycarbonate vectors. The impact of different functions (morpholino-, guanidinium-, hydrophobic groups) of the architecture (linear homopolymer to dumbbell-shape) and of the molecular weight of these copolymers on their capacity to form polyplexes and to decrease the expression of two epigenetic regulators of gene expression, HDAC7 and HDAC5, was evaluated. The use of one of these polymers combining morpholine and guanidine functions at the ratio >1 and hydrophobic trimethylene carbonate groups showed a significant decrease of mRNA and protein level in HeLa cells, similar to PEI. These results highlight the potential of polycarbonate vectors for future in vivo application as an anticancer therapy.
Mots clés
Carbonates, chemistry, Gene Expression, Gene Knockdown Techniques, HeLa Cells, Histone Deacetylases, genetics, Humans, Polymers, chemistry, RNA Interference, RNA, Small Interfering, genetics, Transfection
Référence
Biomacromolecules. 2015 Mar;16(3):769-79