Impact of Linker Groups on Self-Assembly, Gene Transfection, Antibacterial Activity, and In Vitro Cytotoxicity of Cationic Bolaamphiphiles

Cationic bolaamphiphiles have gained significant attention in various research fields, including materials science, drug delivery, and gene therapy, due to their unique properties and potential applications. The objective of the current research is to develop more effective cationic bolaamphiphiles. Thus, we have designed and synthesized two cationic bolaamphiphiles (-(CH2)(12)(2,3-dihydroxy-N,N-dimethyl-N-(3-ureidopropyl)propan-1-aminium chloride))2 (C-12(DDUPPAC)(2))) and (-(CH2)(12)(N-(3-(carbamoyloxy)propyl)-2,3-dihydroxy-N,N-dimethylpropan-1-aminium chloride)2 (C-12(CPDDPAC)(2)) containing urea and urethane linkages, respectively. We have investigated their self-assembly properties in water using several techniques, including surface tension, electrical conductivity, fluorescence probe, calorimetry, dynamic light scattering, and atomic force microscopy. Their biological applications, e.g., in vitro gene transfection, antibacterial activity, and cytotoxicity, were studied. Both bolaamphiphiles were observed to produce aggregates larger than spherical micelles above a relatively low critical aggregation concentration (cac). The calorimetric experiments suggested the thermodynamically favorable spontaneous aggregation of both bolaforms in water. The results of interaction studies led to the conclusion that C-12(CPDDPAC)(2) binds DNA with a greater affinity than C-12(DDUPPAC)(2). Also, C-12(CPDDPAC)2 is found to act as a more efficient gene transfection vector than C-12(DDUPPAC)(2) in 264.7 cell lines. The in vitro cytotoxicity assay using MTT, however, revealed that neither of the bolaamphiphiles was toxic, even at higher quantities. Additionally, both bolaforms show beneficial antibacterial activity.