title: Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials.
abstract: Bacterial resistance to antimicrobials is a global threat that requires development of innovative therapeutics that circumvent its onset. The use of Transcription Factor Decoys (TFDs), DNA fragments that act by blocking essential transcription factors in microbes, represents a very promising approach. TFDs require appropriate carriers to protect them from degradation in biological fluids and transfect them through the bacterial cell wall into the cytoplasm, their site of action. Here we report on a bolaform cationic surfactant, [12-bis-THA]Cl2, with proven transfection activity in vivo. By studying the physical-chemical properties of its aqueous solutions with light scattering, cryo-TEM, ζ-potential, absorption and fluorescence spectroscopies, we prove that the bolaamphiphiles associate into transient vesicles which convert into one-dimensional elongated structures over time. These surfactant assemblies complex TFDs with extremely high efficiency, if compared to common cationic amphiphiles. At Z+/-=11, the nanoplexes are stable and have a size of 120nm, and they form independently of the original morphology of the [12-bis-THA]Cl2 aggregate. DNA is compacted in the nanoplexes, as shown through CD spectroscopy and fluorescence, but is readily released in its native form if sodium taurocholate is added.
authors.affiliation: Department of Chemistry "Ugo Schiff" and CSGI, University of Florence. Via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Mamusa
authors.affiliation: Department of Chemistry "Ugo Schiff" and CSGI, University of Florence. Via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Resta
authors.affiliation: Nanovector s.r.l. Via Livorno 60, 10144 Torino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Barbero
authors.affiliation: Procarta Biosystems Ltd. Innovation Centre, Norwich Research Park, Norwich NR4 7GJ, UK; Biological Chemistry Department, John Innes Centre, Norwich NR4 7UH, UK.
authors.forename: Davide
authors.initials: D
authors.lastname: Carta
authors.affiliation: Procarta Biosystems Ltd. Innovation Centre, Norwich Research Park, Norwich NR4 7GJ, UK; Kuecept Ltd. 16/17 Station Close, Potters Bar EN6 1TL, UK.
authors.forename: Doroty
authors.initials: D
authors.lastname: Codoni
authors.affiliation: Procarta Biosystems Ltd. Innovation Centre, Norwich Research Park, Norwich NR4 7GJ, UK; School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Kostas
authors.initials: K
authors.lastname: Hatzixanthis
authors.affiliation: Procarta Biosystems Ltd. Innovation Centre, Norwich Research Park, Norwich NR4 7GJ, UK; Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: McArthur
authors.affiliation: Department of Chemistry "Ugo Schiff" and CSGI, University of Florence. Via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy. Electronic address: debora.berti@unifi.it.
authors.forename: Debora
authors.initials: D
authors.lastname: Berti
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D011485:Protein Binding; D011728:Pyridones / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D013619:Tacrine / Q000031:analogs & derivatives*; D013656:Taurocholic Acid / Q000737:chemistry; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014162:Transfection
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D005663:Furans; D009841:Oligonucleotides; D011728:Pyridones; D013501:Surface-Active Agents; D014157:Transcription Factors; C543575:bolaamphiphile; D013619:Tacrine; D013656:Taurocholic Acid; D004247:DNA
keywords: Bacterial resistance; Bolaamphiphile; Circular dichroism; DNA delivery; Light scattering; Transcription factor decoy