Cyclen-based cationic lipids with double hydrophobic tails for efficient gene delivery

Abstract

The gene transfection abilities and structure–activity relationship of newly designed cationic lipids were studied in detail.

Recent progress in gene therapy to deliver nucleic acids with multivalent cationic vectors

“…Other groups have reported the electrostatic interaction when the GCL contains an oligo-oxyethylene spacer [93,115], and/or other headgroups as imidazolium or pyridinium [45, 57-59, 75, 99, 116]. Looking for more biocompatible vectors, GCLs that incorporate aminoacid rests, such as GCL-lysine 12 based and GCL-arginine based [60,62,64], GCL-cholesterol based [117][118][119], and GCL-cyclen-based [120] have been also investigated. Lipoplexes containing a MVCL with dendritic-type headgroup have been also analyzed [67,121,122].…”

“…TEM and/or cryo-TEM studies have reported many micrographs to characterize the size, shape, and morphology of a wide variety of lipoplexes as: (a) pDNA with GCLs [45,54,57,62,64,75,93,115,117,118,120], MVCLs [63], cationic polymers [107,133,[169][170][171] or polycations [40,84,100,136]; and (b) siRNA with cationic polymers [90,104]. Fig.…”

“…As a result of that, the transfection capability [75]. Recent studies reporting TE of lipoplexes and polyplexes have been investigated: (i) divalent GCLs, as cholesterol-based with alkyl or oligooxyethylene spacers [118,119,121], aromatic-based with alkyl or oligo-oxyethylene spacers [46,93], SS14 linkers [66], ammonium with alkyl or oligo-oxyethylene spacers [54,71,93,179], imidazolium or pyridinium derivatives with alkyl-or oligooxyethylene spacers [45,59,75], aminoacid-based [62,64] or gemini-like amphiphilic peptides [150], cyclen-based CLs [120,180], and archael tetraether-based lipids [138];…”

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

“…17 In our previous studies, we have demonstrated the potential of cyclen-based gene delivery systems. 11,12,16 On the other hand, lipids with monounsaturated hydrophobic chain(s) (e.g., oleyl group) might facilitate the transfection, since they could facilitate membrane disruption and DNA escape from endosome by increasing the membrane fluidity. 8 Many oleyl-contained lipids have been proved to be efficient delivery materials, 8,12 and some commercially available transfection reagents also have oleyl moiety in their structures.…”

“…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.…”