Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials
Marianna Mamusa, Claudio Resta, Francesco Barbero, Davide Carta, Doroty Codoni, Kostas Hatzixanthis, Michael McArthur, Debora Berti
Colloids and Surfaces B: Biointerfaces
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 120 nm, and they form independently of the original morphology of the [12-bis-THA]Cl2aggregate. 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.
Circular dichroism, Secondary structure, Ligand binding, Biochemistry, Materials