Hydroxyl-containing non-viral lipidic gene vectors with macrocyclic polyamine headgroups

Cationic lipids are the most widely used non-viral gene vectors, and it is important to develop novel lipids that have high transfection efficiency (TE) and good biocompatibility. A series of macrocyclic polyamine (cyclen and TACN)-based cationic lipids bearing different hydrophobic tails were synthesized with the ring-opening reaction. Several assays were used to study their interactions with plasmid DNA, and these lipoplexes could efficiently condense DNA into nanoparticles with proper sizes and zeta potentials. CCK-8-based cell viability assays showed relatively lower cytotoxicity of the lipoplexes compared with the commercially available Lipofectamine 2000. With transfection in vitro, lipid 6a had comparable or better TE than Lipofectamine 2000 in both 7402 and A549 cells. Interestingly, the TE of 6a was significantly increased in the presence of serum. The results not only demonstrate that lipid 6a can be a promising non-viral gene vector, they also provide clues for developing cationic gene vectors for future in vivo applications.