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Synthesis of poly(meth)acrylates with thioether and tertiary sulfonium groups by ARGET ATRP and their use as siRNA delivery agents.

Identifieur interne : 000295 ( Main/Exploration ); précédent : 000294; suivant : 000296

Synthesis of poly(meth)acrylates with thioether and tertiary sulfonium groups by ARGET ATRP and their use as siRNA delivery agents.

Auteurs : Matthew C. Mackenzie [États-Unis] ; Arun R. Shrivats ; Dominik Konkolewicz ; Saadyah E. Averick ; Michael C. Mcdermott ; Jeffrey O. Hollinger ; Krzysztof Matyjaszewski

Source :

RBID : pubmed:25515324

Descripteurs français

English descriptors

Abstract

The field of RNA interference depends on the development of safe and efficient carriers for short interfering ribonucleic acid (siRNA) delivery. Conventional cationic monomers for siRNA delivery have utilized the nitrogen heteroatom to produce cationic charges. Here, we polymerized cationic sulfonium (meth)acrylate by activators regenerated by electron transfer (ARGET) atom transfer radical polymerization (ATRP) to form polymers with narrow molecular weight distributions for siRNA delivery. The tertiary sulfonium species was stable toward dealkylation in water but less stable in the polar aprotic solvent dimethyl sulfoxide. Block copolymers poly(ethylene oxide) with poly(meth)acrylate containing sulfonium moieties were prepared as an siRNA delivery platform. Results suggested block copolymers were biocompatible up to 50 μg/mL in vitro and formed polyplexes with siRNA. Additionally, block copolymers protected siRNAs against endonuclease digestion and facilitated knockdown of glyceraldehyde 3-phosphate dehydrogenase (Gapdh) mRNA expression in murine calvarial preosteoblasts. The versatility, biocompatibility, and cationic nature of these tertiary sulfonium groups are expected to find widespread biological applications.

DOI: 10.1021/bm501449a
PubMed: 25515324


Affiliations:


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