Biotinylated Cyclen‐Contained Cationic Lipids as Non‐Viral Gene Delivery Vectors

Abstract

A series of 1, 4, 7, 10-tetraazacyclododecane (cyclen)-based cationic lipids, namely 5a-c bearing a biotin moiety and a variety of end groups (cholesterol, diosgenin, and α-tocopherol) via biodegradable carbamate bond linkage were prepared and applied as non-viral gene delivery vectors. The liposomes formed from 5 and dioleoylphosphatidylethanolamine could bind and condense plasmid DNA into nanoparticles with appropriate size and zeta potentials. All biotinylated cyclen cationic lipids showed higher cell viability than commercially available lipofectamine 2000 even at high N/P ratios, while their transfection efficiency was relatively lower. Further, results indicate that among the three lipids, α-tocopherol-containing compound 5c has higher DNA-binding ability, lower cytotoxicity, and higher transfection efficiency. Transfection in two different cell lines revealed that these lipoplexes have higher gene delivery efficiency toward tumor cells.

Skeleton-Controlled pDNA Delivery of Renewable Steroid-Based Cationic Lipids, the Endocytosis Pathway Analysis and Intracellular Localization

“…Cho-Arg and 2H-Cho-Arg/pDNA lipoplexes were seen as small nanoparticles (40–110 nm) and Dios-Arg/pDNA were bigger nanoparticles (120–210 nm), whereas Tigo-Arg/pDNA showed the biggest particle sizes of 180–340 nm. Likewise, Yu et al [ 46 ] recently reported that the lipoplexes particle size of a biotin-conjugated diosgenin cationic lipid were larger than their cholesterol-containing analogs. The trend of steroid-based lipids/pDNA lipoplexes morphology measured by TEM was in accordance with the DLS data.…”

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

“…The toxicity of liposomes and lipoplexes toward HEK293 cells was determined by using the MTT assay following a literature procedure . Approximately 7000 cells per well were seeded into 96‐well plates.…”

“…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.…”

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

“…The samples were sonicated for 5 min in a bath sonicator to generate small unilamellar vesicles at a concentration of 1 mM. 15 …”

“…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.…”