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

Abstract

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.

Cholesterol-Based Compounds: Recent Advances in Synthesis and Applications

“…A series of macrocycle polyamine (cyclen and 1,4,7-triazacyclononane (TACN))-based cationic lipids 85 and 88 , bearing cholesterol as a hydrophobic tail, were synthesized through ring-opening reactions (Scheme 18). These cationic lipids, 85 and 88 , were used in combination with 1,2-dioleoyl- sn -glycero- -3-phosphoethanolamine (DOPE) to prepare lipoplexes, which efficiently condense DNA into nanoparticles with a proper size and zeta potential [25].…”

“…Furthermore, the authors rationalized the good serum tolerance of 85 due to the presence of a hydroxy group in its structure. These promising results indicated that cationic-lipid 85 should be considered for nonviral gene vectors in in vivo applications [25].…”

Transfection by cationic gemini lipids and surfactants

“…It should be mentioned here that cationic surfactants with long linear polyamine chains as head groups can have a low gene delivery efficiency because, as revealed by molecular dynamics simulations, they can undergo self-folding. 89 For this reason, the cyclic polyamine cyclen has recently emerged as an alternative multivalent head group, 90 and its pseudoglyceryl derivatives 12 91 are shown here (Chart 3). As the mono-oleyl derivative 12a was less active and more toxic than the cholesterol analogue 12b, further examples of combinations of cyclens with other structural moieties will be discussed in the relevant sections.…”

Multi-functionalized graphene oxide complex as a plasmid delivery system for targeting hepatocellular carcinoma therapy

“…(5) The amino end of GO-PEI-PEG was connected to FA to produce the nal composite GO-PEI-PEG-FA. (6) The negatively charged si-Stat3 was loaded on the positively charged GO-PEI-PEG-FA via electrostatic interaction.…”