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Impact of the Structure of Biocompatible Aliphatic Polycarbonates on siRNA Transfection Ability

2015; American Chemical Society; Volume: 16; Issue: 3 Linguagem: Inglês

10.1021/bm501676p

1526-4602

Antoine Frère, Michał Kawalec, Sarah Tempelaar, Paul Peixoto, Elodie Hendrick, Olivier Peulen, Brigitte Évrard, Philippe Dúbois, Laetitia Mespouille, Denis Mottet, Géraldine Piel,

biodegradable polymer synthesis and properties

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.