title: Influence of oligospermines architecture on their suitability for siRNA delivery.
abstract: Spermines are naturally abundant polyamines that partially condense nucleic acids and exhibit the proton-sponge effect in an acidic environment. However, spermines show a limited efficiency for transfecting nucleic acids because of their low molecular weight. Therefore, spermines need to be modified to be used as nonviral vectors for nucleic acids. Here, we synthesized linear bisspermine as well as a linear and dendritic tetraspermine with different molecular architectures. These oligospermines were self-assembled into polyplexes with siRNA. The structure-activity relationship of the oligospermines was evaluated in terms of their efficiency for delivering siRNA into a nonsmall cell lung carcinoma cell line. Oligospermines displayed minimal cytotoxicity but efficient siRNA condensation and showed better stability against polyanions than polyethylenimine. The morphology of the polyplexes was strongly affected by the oligospermine architecture. Linear tetraspermine/siRNA polyplexes showed the best gene-silencing efficiency among the oligospermines tested at both the mRNA and protein expression levels, indicating the most favorable structure for siRNA delivery.
authors.affiliation: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , 259 Mack Avenue, Detroit, Michigan 48201, United States.
authors.forename: Maha
authors.initials: M
authors.lastname: Elsayed
authors.forename: Vincent
authors.initials: V
authors.lastname: Corrand
authors.forename: Vidula
authors.initials: V
authors.lastname: Kolhatkar
authors.forename: Yuran
authors.initials: Y
authors.lastname: Xie
authors.forename: Na Hyung
authors.initials: NH
authors.lastname: Kim
authors.forename: Rohit
authors.initials: R
authors.lastname: Kolhatkar
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Merkel
mesh_terms: D000838:Anions / Q000737:chemistry; D001667:Binding, Competitive; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D060326:Chemistry Techniques, Synthetic; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000493:pharmacokinetics / Q000633:toxicity; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D013096:Spermine / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
chemical_list: D000838:Anions; D034741:RNA, Small Interfering; D013096:Spermine; D006493:Heparin