title: Synthesis of poly(meth)acrylates with thioether and tertiary sulfonium groups by ARGET ATRP and their use as siRNA delivery agents.
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.
authors.affiliation: Department of Chemistry, Carnegie Mellon University , 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Mackenzie
authors.forename: Arun R
authors.initials: AR
authors.lastname: Shrivats
authors.forename: Dominik
authors.initials: D
authors.lastname: Konkolewicz
authors.forename: Saadyah E
authors.initials: SE
authors.lastname: Averick
authors.forename: Michael C
authors.initials: MC
authors.lastname: McDermott
authors.forename: Jeffrey O
authors.initials: JO
authors.lastname: Hollinger
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Matyjaszewski
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D002460:Cell Line; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D051379:Mice; D018625:Microscopy, Atomic Force / Q000379:methods*; D008855:Microscopy, Electron, Scanning / Q000379:methods*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011092:Polyethylene Glycols; D011109:Polymethacrylic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D012886:Skull / Q000166:cytology; D013452:Sulfonium Compounds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D011109:Polymethacrylic Acids; D034741:RNA, Small Interfering; D013452:Sulfonium Compounds; D011092:Polyethylene Glycols; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases