Influence of Minor Backbone Structural Variations in Modulating the in Vitro Gene Transfer Efficacies of α-Tocopherol Based Cationic Transfection Lipids

Abstract

Toward probing the influence of backbone structural variation in cationic lipid mediated gene delivery of α-tocopherol based lipids, two novel α-tocopherol based lipids 1 and 2 have been designed and synthesized. The only structural difference between the cationic amphiphiles 1 and 2 is the backbone structure, where lipid 1 has a non-glycerol backbone and lipid 2 has a glycerol backbone. The lipids 1 and 2 showed contrasting transfection efficiencies: lipid 1 showed high gene transfer efficacy in multiple cultured animals cell lines, whereas lipid 2 is transfection incompetent. In summary, the present findings demonstrate that in the case of α-tocopherol based lipids even minor structural variations like backbone can profoundly influence size, DNA binding characteristics, cellular uptake, and consequently gene delivery efficacies.

Cyclen-based double-tailed lipids for DNA delivery: Synthesis and the effect of linking group structures

“…Such advantage of symmetric structures was also confirmed by some other studies. 9,22 It's known that TE was influenced not only by the chemical structure of the carrier, but also by the cell type. Thus we applied L1 to the gene delivery toward various other cell lines (7402, U-2OS, and HepG-2 cells), the results are shown in Figure S2.…”

“…3 Since Felgner and co-workers in 1987 first reported cationic lipid DOTMA for gene delivery, 5 an upsurge of global interest has been witnessed in the design and synthesis of novel efficient cationic transfection lipids. 6 A number of structure-activity relationship studies have demonstrated that each building block of the lipids, including positive charged polar head group, 7 hydrophobic tails, [8][9][10][11][12] linking group, [13][14][15][16] would largely influence the TEs of the delivery materials.…”

“…Kedika and Patri found that the lipid with symmetrical backbone might give much higher TE than those with asymmetrical backbone structure. 9 More recently, Niyomtham et al revealed that the spermine-based cationic lipids with diverse central core structures had much different TEs. 20 Considering this, herein we design and synthesize a series of cationic lipids with cyclen as cationic headgroup and oleyl as hydrophobic tails.…”

Reducible Amino Acid Based Cationic Lipids as Highly Efficient and Serum‐Tolerant Gene Vectors

“…The natural amino acids histidine and lysine were chosen as the headgroups because of the respectable buffering capacity of the former and the gene‐packing ability of the latter . The naturally occurring α‐tocopherol (a form of vitamin E) was chosen as the hydrophobic tail because of its good biocompatibility and use in a wide range of drug delivery systems . The interaction between DNA and liposomes formed from these lipids was investigated.…”

Effects of heterocyclic-based head group modifications on the structure–activity relationship of tocopherol-based lipids for non-viral gene delivery

“…Earlier, cationic conjugates of tocopherol pertaining to gemini lipids, hydroxyethyl bearing head groups and glycerol and non-glycerol based backbones were synthesized for structureactivity investigations (25,26,27). In recent years, it has been shown by othergroups that progress can be achieved via heterocyclic cationic lipids (28,29).…”