Journal
BIOMACROMOLECULES
Volume 16, Issue 3, Pages 769-779Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bm501676p
Keywords
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Funding
- Belgium National Fund for Scientific Research
- TELEVIE
- Centre Anti-Cancereux
- Fonds Leon Fredericq pres de l'Universite de Liege
- Belgian Federal Government Office Policy of Science (SSTC)
- European Commission
- Wallonia Region (FEDER Program)
- OPTI2MAT program of excellence
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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.
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