Solid phase synthesis of novel asymmetric hydrophilic head cholesterol-based cationic lipids with potential DNA delivery

Radchatawedchakoon, Widchaya; Watanapokasin, Ramida; Krajarng, Aungkana; Yingyongnarongkul, Boon‐ek

doi:10.1016/j.bmc.2009.10.057

Cited by 22 publications

(19 citation statements)

References 33 publications

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“…The transfection efficiency of the cationic liposome also depends on the cationic lipisomes/DNA ratio as previously reported by our group 19,33,34) and others. [35][36][37] To find out the optimal liposomes/DNA ratio, transfection experiments were performed against HEK293 cells by using mixture lipids/ DOPE ratio of 1 : 1.…”

Section: )supporting

confidence: 76%

“…19,33,34) To evaluate the transfection efficiency of these mixture lipids toward the different cell lines, human breast adenocarcinoma (MCF-7) and cervical epithelial adenocarcinoma (HeLa) cells, the experiments were performed by using optimum condition under serum-free conditions. The transfection efficiency of mixture lip- ids was compared with the commercially available transfection agent, Lipofectamine 2000, which was calculated as 100%.…”

Section: )mentioning

confidence: 99%

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Synergistic Effect of Cationic Lipids with Different Polarheads, Central Core Structures and Hydrophobic Tails on Gene Transfection Efficiency

Niyomtham

Apiratikul

Chanchang

et al. 2014

Biological & Pharmaceutical Bulletin

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Lipid-mediated delivery of DNA into cells holds great promise both for gene therapy and basic research applications. The primary approach to improving transfection efficiency is the design and synthesis of novel cationic lipids. Alternatively, using the synergistic effect of different cationic mixtures can provide another approach to increasing transfection efficiency. This paper describes the synergistic effect of lipids with different polarheads, central core structures and hydrophobic tails. The enhancement of cellular transfection into HEK293 cells was observed by combining two lipids having aminoglycerol and di(hydroxylethyl)amino core structures at a 1 : 1 weight ratio. Additionally, the liposome formation of these lipids with the helper lipid, 1,2-dioleoyl-propyl-3-phosphatidylethanolamine (DOPE), at the weight ratio of 1 : 1 can provide higher transfection efficiency into HEK293, MCF-7 and HeLa cells than Lipofectamine™ 2000. Our finding indicated that cationic liposomes comprised of a mixture of lipids with different polarheads, central core structures and hydrophobic tails should be very promising in liposome-mediated gene delivery in vitro and in vivo.Key words cationic liposome; synergistic effect; DNA delivery; non-viral vector.Gene therapy has gained significant attention over past two decades as an alternative method to treat genetic disorders 1,2) as well as cancers.3) One fundamental of gene therapy is the delivery system that can introduce and stabilize genetic material. Since free oligonucleotides and DNA are rapidly degraded by serum nucleases, 4) many efforts are focused on developing the carriers to protect and deliver these materials into targeted cells. Two delivery systems namely viral and non-viral vectors are currently developed to solve the problems. Viral carriers have known to be one of the most effective gene delivery methods for in vivo application. [5][6][7][8] Over one thousand gene therapy clinical trials have been completed or approved; two-thirds of which performed by viral vectors. 8)However, the limitation of viral vectors concerning toxicity, immunogenicity, scale-up procedures and their relatively small capacity for therapeutic DNA has prompted the development non-viral vectors. Delivery systems based on non-viral vectors, for example cationic lipids, dendrimers or cationic polymers, have been the focus of much recent research.9) Non-viral systems have proved to be generally less toxic or immunogenic, more easily to produce and a greater stability.Cationic liposomes are one of the most extensively studied of non-viral vectors because of their lesser immunogenic nature, ease of production and handle, and ability to deliver large pieces of DNA. Cationic liposomes, like other non-viral vectors bearing positive charge, interact with the negatively charged phosphate backbone of nucleic acids to form a compact structure and facilitate cellular uptake by endocytic routes. [10][11][12][13] Since the first application of cationic lipid in DNA delivery, 14) numerous cationic lipids...

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Section: )supporting

confidence: 76%

Section: )mentioning

confidence: 99%

Synergistic Effect of Cationic Lipids with Different Polarheads, Central Core Structures and Hydrophobic Tails on Gene Transfection Efficiency

Niyomtham

Apiratikul

Chanchang

et al. 2014

Biological & Pharmaceutical Bulletin

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“…[22,24,30] To find out the optimal ratio of each lipid, transfection experiments were performed against HEK293 cells by using optimal lipid/DOPE ratio of each compound, as shown in Figure 3. The optimal N/P ratios are shown in Figure 4.…”

Section: Transfection Biologymentioning

confidence: 99%

High Transfection Efficiency of Cationic Lipids with Asymmetric Acyl–Cholesteryl Hydrophobic Tails

Radchatawedchakoon

Krajarng

Niyomtham

et al. 2011

Chemistry A European J

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The ability of a nonviral gene delivery system to overcome extra- and intracellular barriers is a critical issue for the future clinical applications of gene therapy. In recent years much effort has been focused on the development of a variety of DNA carriers, and cationic liposomes have become the most common nonviral gene delivery system. One hundred and eighty novel cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails were synthesized by parallel solid-phase chemistry. The liposomes were prepared and gel retardation assays were used to study the binding efficiency between the prepared liposome and the DNA. Transfection efficiencies of the lipids were evaluated against various mammalian cells, such as human embryonic kidney (HEK293), human cervical adenocarcinoma (HeLa), canine osteosarcoma (D17), colorectal adenocarcinoma (COLO 205), and human prostate adenocarcinoma (PC3) cells. The lipids with an acyl portion at the terminal part of the polyamine backbone exhibited higher transfection efficiency than those with the acyl portion as an internal part of the backbone. These compounds also showed higher transfection efficiency and lower cytotoxicity than the commercially available agents, Effectene, DOTAP, and DC-Chol.

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“…Guanidines have the extra advantage, being bidentate, of being able to form two hydrogen bonds with negatively charged groups e.g., carboxylates, phosphates or sulfates present on the carbohydrates associated with the cell membrane, and this advantage has been used in vectors e.g., R8, Arg 8 [11,12] to transport cargoes across cell membranes. These characteristics led to the design of many non-viral vectors for DNA and siRNA, varying from cationic lipids incorporating guanidine head-groups [13-15] e.g., AtuFECT [15], to cationic polymers [16,17] and dendrimers [18,19], to carbohydrate derivatives [19,20], and hydrogels of guanidinylated hyaluronic acid [21]. The use of guanidinium-containing lipid based carriers for gene delivery dates back to 1996 where Lehn et al synthesized two guanidinium cholesterol lipids: bis-guanidiniumspermidine-cholesterol (BGSC) and bis-guanidinium-trencholesterol (BGTC), each containing two guanidine groups, which were synthesized and evaluated for their DNA transfection efficiencies in eukaryotic cells (Figure 1) [22] where they were found to be efficient DNA transfecting agents.…”

Section: Introductionmentioning

confidence: 99%

Self-Assembled Lipoplexes of Short Interfering RNA (siRNA) Using Spermine-Based Fatty Acid Amide Guanidines: Effect on Gene Silencing Efficiency

Metwally

Blagbrough

2011

Pharmaceutics

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Four guanidine derivatives of N4, N9-diacylated spermine have been designed, synthesized, and characterized. These guanidine-containing cationic lipids bound siRNA and formed nanoparticles. Two cationic lipids with C18 unsaturated chains, N1,N12-diamidino-N4, N9-dioleoylspermine and N1,N12-diamidino-N4-linoleoyl-N9-oleoylspermine, were more efficient in terms of GFP expression reduction compared to the other cationic lipids with shorter C12 (12:0) and very long C22 (22:1) chains. N1,N12-Diamidino-N4-linoleoyl-N9-oleoylspermine siRNA lipoplexes resulted in GFP reduction (26%) in the presence of serum, and cell viability (64%). These data are comparable to those obtained with TransIT TKO. Thus, cationic lipid guanidines based on N4, N9-diacylated spermines are good candidates for non-viral delivery of siRNA to HeLa cells using self-assembled lipoplexes.

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Solid phase synthesis of novel asymmetric hydrophilic head cholesterol-based cationic lipids with potential DNA delivery

Cited by 22 publications

References 33 publications

Synergistic Effect of Cationic Lipids with Different Polarheads, Central Core Structures and Hydrophobic Tails on Gene Transfection Efficiency

Synergistic Effect of Cationic Lipids with Different Polarheads, Central Core Structures and Hydrophobic Tails on Gene Transfection Efficiency

High Transfection Efficiency of Cationic Lipids with Asymmetric Acyl–Cholesteryl Hydrophobic Tails

Self-Assembled Lipoplexes of Short Interfering RNA (siRNA) Using Spermine-Based Fatty Acid Amide Guanidines: Effect on Gene Silencing Efficiency

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