The synthesis of cholesterol-based cationic lipids with trimethylamine head and the effect of spacer structures on transfection efficiency

Kim, Bieong-Kil; Bae, Yun-Ui; Doh, Kyung-Oh; Hwang, Guen-Bae; Lee, Sung-Hye; Kang, Hyungu; Seu, Young‐Bae

doi:10.1016/j.bmcl.2011.04.071

Cited by 16 publications

(17 citation statements)

References 16 publications

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“…Ether linkers in a cholesterol backbone are known to be more efficient for gene delivery than other linkage types [16,17]. Previously, we showed that alterations to the carbon length and electron-rich π-bond in the spacer between the amine head and cholesterol backbone have profound effects on transfection efficiency [18]. We found that ether-linked lipids were more effective in the delivery of genes compared to carbamoyl-linked lipids with the same head group (lipids A and B ).…”

Section: Discussionmentioning

confidence: 99%

“…Ether linkage in a cholesterol backbone is more efficient than other linkage types for gene delivery [16,17]. Efficient gene delivery of quaternary ammonium cationic lipids by using a cholesterol backbone and an ether linkage has been reported previously [18–20]. The hydrophobic domains are generally long-chain fatty acids or a cholesterol derivative.…”

Section: Introductionmentioning

confidence: 99%

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Efficient Delivery of Plasmid DNA Using Cholesterol-Based Cationic Lipids Containing Polyamines and Ether Linkages

Kim

Seu

Bae

et al. 2014

IJMS

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Cationic liposomes are broadly used as non-viral vectors to deliver genetic materials that can be used to treat various diseases including cancer. To circumvent problems associated with cationic liposome-mediated delivery systems such as low transfection efficiency and serum-induced inhibition, cholesterol-based cationic lipids have been synthesized that resist the effects of serum. The introduction of an ether-type linkage and extension of the aminopropyl head group on the cholesterol backbone increased the transfection efficiency and DNA binding affinity compared to a carbamoyl-type linkage and a mono aminopropyl head group, respectively. Under optimal conditions, each liposome formulation showed higher transfection efficiency in AGS and Huh-7 cells than commercially available cationic liposomes, particularly in the presence of serum. The following molecular structures were found to have a positive effect on transfection properties: (i) extended aminopropyl head groups for a strong binding affinity to plasmid DNA; (ii) an ether linkage that favors electrostatic binding to plasmid DNA; and (iii) a cholesterol backbone for serum resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficient Delivery of Plasmid DNA Using Cholesterol-Based Cationic Lipids Containing Polyamines and Ether Linkages

Kim

Seu

Bae

et al. 2014

IJMS

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“…[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. As shown in Fig.…”

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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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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“…The interest in gemini surfactants is widely recognized in several areas ranging from gene therapy [1][2][3][4][5][6], drug delivery [2,7], and antibacterial treatments [8,9] to industrial applications [10][11][12][13][14]. The amount of information and work developed in the last few years has also given rise to a vast number of review papers on the topic [6,[15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

The role of excluded volume and electrostatics from coarse-grain modeling of the interaction of gemini surfactants with like-charged membranes

Nunes¹,

Almeida²,

Dias³

et al. 2012

Molecular Physics

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Cationic systems composed of lipids and/or surfactants are of paramount importance in a variety of applications. Within these, gemini have attracted particular attention, mainly due to their improved aggregation properties and to the possibility of tuning offered by the presence of a spacer. In this work, a Monte Carlo simulation study with a coarse-grained model was employed to assess the interaction of cationic gemini surfactants with a like-charged model membrane. Separating the contribution of the excluded volume and that of the electrostatic effects in the organization of gemini-lipid membranes was the first goal of this work and the role of these factors was assessed varying the concentration, the spacer length and the headgroup charge of gemini surfactants. The results provide a new insight on the organization of lipid headgroups in the vicinity of gemini surfactants. It was found that the surfactant-lipid interaction is strongly affected by the surfactant spacer length, being controlled by an overall balance between excluded volume and surfactant-lipid and surfactant-surfactant electrostatic effects. It is also seen that the out-of-plane motion of the spacer has a significant effect upon membrane organization and counterion condensation. Good agreement was found with results previously obtained from atomistic simulation.

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The synthesis of cholesterol-based cationic lipids with trimethylamine head and the effect of spacer structures on transfection efficiency

Cited by 16 publications

References 16 publications

Efficient Delivery of Plasmid DNA Using Cholesterol-Based Cationic Lipids Containing Polyamines and Ether Linkages

Efficient Delivery of Plasmid DNA Using Cholesterol-Based Cationic Lipids Containing Polyamines and Ether Linkages

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

The role of excluded volume and electrostatics from coarse-grain modeling of the interaction of gemini surfactants with like-charged membranes

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