title: Amino Acid-Functionalized Dendritic Polyglycerol for Safe and Effective siRNA Delivery.
abstract: The development of safe and effective delivery vectors is a great challenge for the medicinal application of RNA interference (RNAi). In this study, we aimed to develop new synthetic transfection agents based on dendritic polyglycercol (dPG), which has shown great biocompatibility in several biomaterial applications. Histidine and aromatic amino acids were conjugated to the amine-terminated dPGs through amide bonds. We systematically tuned the amino acid combination, functionalization ratio, ligand density, and dPG core size to find optimal vectors. It was found that histidine-tryptophan-functionalized dPGs exhibited improved delivery efficiency and greatly reduced toxicity over simple amine-terminated dPGs. Furthermore, the optimized vectors exhibited strong siRNA binding and high transfection efficiency in serum containing media. The results indicate that the current amino acid-functionalized dPG system is a promising candidate for in vivo siRNA delivery applications.
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697-2025, United States.
authors.forename: Hanxiang
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin , Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Cathleen
authors.initials: C
authors.lastname: Schlesener
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697-2025, United States.
authors.forename: Olivia
authors.initials: O
authors.lastname: Cromwell
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin , Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hellmund
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin , Takustrasse 3, 14195, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.affiliation: Department of Chemistry, University of California , Irvine, California 92697-2025, United States.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Guan
mesh_terms: D000818:Animals; D003470:Culture Media / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D015870:Gene Expression; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006639:Histidine / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D003470:Culture Media; D050091:Dendrimers; D011108:Polymers; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; C043941:polyglycerol; D006639:Histidine; D014364:Tryptophan; D005990:Glycerol