title: Glycine-terminated dendritic amphiphiles for nonviral gene delivery.
abstract: Development of nonviral vectors for the successful application of gene therapy through siRNA/DNA transfection of cells is still a great challenge in current research. (1, 2)  In the present study, we have developed multivalent polyglycerol dendron based amphiphiles with well-defined molecular structures that express controlled glycine arrays on their surfaces. The structure-activity relationships with respect to the siRNA complexation, toxicity, and transfection profiles were studied with synthesized amphiphilic polycations. Our findings revealed that a second-generation amphiphilic dendrimer (G2-octaamine, 4) that has eight amine groups on its surface and a hydrophobic C-18 alkyl chain at the core of the dendron, acts as an efficient vector to deliver siRNA and achieve potent gene silencing by investigating the knockdown of luciferase and GAPDH gene activity in HeLa cells. Interestingly, the amphiphilic vector is nontoxic even at higher ratio of N/P 100. To the best of our knowledge this is the first example of successful in vitro siRNA transfection using dendritic amphiphiles. We believe that this supramolecular complex may serve as a new promising alternative for nonviral siRNA delivery systems and will be investigated for in vivo siRNA delivery in the future.
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Berlin, Germany.
authors.forename: Shashwat
authors.initials: S
authors.lastname: Malhotra
authors.forename: Hannah
authors.initials: H
authors.lastname: Bauer
authors.forename: Ariane
authors.initials: A
authors.lastname: Tschiche
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Staedtler
authors.forename: Andreas
authors.initials: A
authors.lastname: Mohr
authors.forename: Marcelo
authors.initials: M
authors.lastname: Calderón
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.forename: Lena
authors.initials: L
authors.lastname: Hoeke
authors.forename: Soroush
authors.initials: S
authors.lastname: Sharbati
authors.forename: Ralf
authors.initials: R
authors.lastname: Einspanier
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002627:Chemistry, Physical; D004247:DNA / Q000737:chemistry / Q000235:genetics; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005998:Glycine / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D050091:Dendrimers; D034741:RNA, Small Interfering; D013501:Surface-Active Agents; D004247:DNA; D005998:Glycine