title: Synthesis of multifunctional PAMAM-aminoglycoside conjugates with enhanced transfection efficiency.
abstract: The development of multifunctional vectors for efficient and safe gene delivery is one of the major challenges for scientists working in the gene therapy field. In this context, we have designed a novel type of aminoglycoside-rich dendrimers with a defined structure based on polyamidoamine (PAMAM) in order to develop efficient, nontoxic gene delivery vehicles. Three different conjugates, i.e., PAMAM G4-neamine, -paromomycin, and -neomycin, were synthesized and characterized by nuclear magnetic resonance (NMR) and MALDI analysis. The conjugates were found to self-assemble electrostatically with plasmid DNA, and unlike neamine conjugate, each at its optimum showed increased gene delivery potency compared to PAMAM G4 dendrimer in three different cell lines, along with negligible cytotoxicity. These results all disclosed aminoglycosides as suitable functionalities for tailoring safe and efficient multifunctional gene delivery vectors.
authors.affiliation: Department of Chemistry, Materials, and Chemical Engineering "G. Natta", Politecnico di Milano , via Mancinelli 7, 20131 Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ghilardi
authors.forename: Daniele
authors.initials: D
authors.lastname: Pezzoli
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Bellucci
authors.forename: Chiara
authors.initials: C
authors.lastname: Malloggi
authors.forename: Armando
authors.initials: A
authors.lastname: Negri
authors.forename: Aurora
authors.initials: A
authors.lastname: Sganappa
authors.forename: Gabriella
authors.initials: G
authors.lastname: Tedeschi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Candiani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Volonterio
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D050091:Dendrimers / Q000737:chemistry*; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008968:Molecular Conformation; D009757:Nylons / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D000617:Aminoglycosides; D050091:Dendrimers; D009757:Nylons; C520550:PAMAM-G4