title: Dendritic polyglycerols with oligoamine shells show low toxicity and high siRNA transfection efficiency in vitro.
abstract: RNA interference provides great opportunities for treating diseases from genetic disorders, infection, and cancer. The successful application of small interference RNA (siRNA) in cells with high transfection efficiency and low cytotoxicity is, however, a major challenge in gene-mediated therapy. Several pH-responsive core shell architectures have been designed that contain a nitrogen shell motif and a polyglycerol core, which has been prepared by a two-step protocol involving the activation of primary and secondary hydroxyl groups by phenyl chloroformate and amine substitution. Each polymer was analyzed by particle size and ζ potential measurements, whereas the respective polyplex formation was determined by ethidium bromide displacement assay, atomic force microscopy (AFM), and surface charge analysis. The in vitro gene silencing properties of the different polymers were evaluated by using a human epithelial carcinoma cell (HeLaS3) line with different proteins (Lamin, CDC2, MAPK2). Polyplexes yielded similar knockdown efficiencies as HiPerFect controls, with comparably low cytotoxicity. Therefore, these efficient and highly biocompatible dendritic polyamines are promising candidates for siRNA delivery in vivo.
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Berlin, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Fischer
authors.forename: Marcelo
authors.initials: M
authors.lastname: Calderón
authors.forename: Andrea
authors.initials: A
authors.lastname: Schulz
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreou
authors.forename: Martin
authors.initials: M
authors.lastname: Weber
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D001483:Base Sequence; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D004996:Ethidium / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D018625:Microscopy, Atomic Force; D009584:Nitrogen / Q000737:chemistry; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D013499:Surface Properties; D014162:Transfection / Q000379:methods*
chemical_list: D050091:Dendrimers; D011073:Polyamines; D011108:Polymers; D034741:RNA, Small Interfering; C043941:polyglycerol; D004996:Ethidium; D009584:Nitrogen; D005990:Glycerol