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Baraldo, Karin; Leforestier, Nicolas; Bureau, M.; Mignet, Nathalie; Scherman, Daniel

doi:10.1023/a:1019894008885

Cited by 14 publications

(3 citation statements)

References 13 publications

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“…Although any cationic agent would be expected to exhibit some toxicity, especially at high concentrations, previous reports have shown that sphingosine forms complexes with DNA and can facilitate transfection. 33 − 36 Considering that sphingosine is a natural degradation product of ceramide that is present in all mammalian cells, 37 , 38 it would be expected that this single-tailed cationic amphiphile might be well-tolerated. Accordingly, we substituted sphingosine for DOTAP in the formulations, and monitored the effect of +/– charge ratio on transfection and toxicity.…”

Section: Resultsmentioning

confidence: 99%

“…Considering the well-known toxicity associated with cationic agents, we investigated the potential to utilize sphingosine, a naturally occurring cationic amphiphile that has been shown to bind DNA and facilitate transfection. 33 − 36 Because sphingosine is generated in lysosomes as a breakdown product of ceramide, cells have mechanisms for degrading/eliminating this molecule, thereby minimizing its toxic effects. 37 , 38 Addition of free, DMSO-solubilized sphingosine to cells is known to activate cathepsin D and trigger apoptosis, but this activation is not observed when sphingosine is incorporated into bilayers.…”

Section: Discussionmentioning

confidence: 99%

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Relating Toxicity to Transfection: Using Sphingosine To Maintain Prolonged Expression in Vitro

Betker

Anchordoquy

2014

Mol. Pharmaceutics

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Cationic reagents are commonly used to facilitate DNA delivery, and transfection experiments are typically initiated in cell culture where the optimal charge ratio is determined. While transfection rates are often enhanced at higher +/– charge ratios, the cellular toxicity associated with the greater amounts of cationic components at elevated charge ratios is often not considered. In addition, the prolonged effects of cationic lipid uptake on cell viability are not evident in a typical 24–48 h transfection experiment. In this study, we compare the transfection efficiency of cationic lipoplexes to effects on viability of cultured cells in both the short and long term (7 days). Our results indicate that, while minimal toxicity is evident 24 h after exposure to DOTAP-based lipoplexes, cell viability continues to decline and ultimately compromises reporter gene expression at longer times. Substitution of a naturally occurring cationic amphiphile, sphingosine, for DOTAP greatly reduces toxicity and allows high expression to be maintained over prolonged periods.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relating Toxicity to Transfection: Using Sphingosine To Maintain Prolonged Expression in Vitro

Betker

Anchordoquy

2014

Mol. Pharmaceutics

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“…It was shown in other works that the charge ratio between cationic liposomes and plasmid DNA strongly affects the size, zeta potential, stability, toxicity, and therefore the transfection efficiency of the lipoplexes [ 35 , 36 , 37 ]. Figure 16 presents the transfection efficiency of cosol_MCLs–pFAR4-luc complexes with different PEG lengths at a charge ratio of 8 or 10.…”

Section: Resultsmentioning

confidence: 99%

Development of Theranostic Cationic Liposomes Designed for Image-Guided Delivery of Nucleic Acid

et al. 2020

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Cationic liposomes have been considered as potential vectors for gene delivery thanks to their ability to transfect cells with high efficiency. Recently, the combination of diagnostic agent and therapeutic agents in the same particle to form a theranostic system has been reported. Magnetic liposomes are one of these examples. Due to the magnetic nanoparticles encapsulated in the liposomes, they can act as a drug delivery system and, at the same time, a magnetic resonance imaging contrast enhancement agent or hyperthermia. In this work, nucleic acid delivery systems based on magnetic cationic liposomes (MCLs) were developed. Two different techniques, reverse phase evaporation and cosolvent sonication, were employed for liposome preparation. Both strategies produced MCLs of less than 200 nm with highly positive charge. Enhancement of their transverse and longitudinal relaxivities r2 and r1 was obtained with both kinds of magnetic liposomes compared to free magnetic nanoparticles. Moreover, these MCLs showed high capacity to form complexes and transfect CT-26 cells using the antibiotic-free pFAR4-luc plasmid. The transfection enhancement with magnetofection was also carried out in CT26 cells. These results suggested that our MCLs could be a promising candidate for image-guided gene therapy.

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Cationic and anionic lipoplexes inhibit gene transfection by electroporation in vivo

Mignet¹,

Vandermeulen²,

Pembouong³

et al. 2010

The Journal of Gene Medicine

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Abstract: The cationic sphingosine/EPC/DNA complexes form weakly compacted structure, potentially labile in vivo, which might be useful for in vivo gene transfer.

Cited by 14 publications

References 13 publications

Relating Toxicity to Transfection: Using Sphingosine To Maintain Prolonged Expression in Vitro

Relating Toxicity to Transfection: Using Sphingosine To Maintain Prolonged Expression in Vitro

Development of Theranostic Cationic Liposomes Designed for Image-Guided Delivery of Nucleic Acid

Cationic and anionic lipoplexes inhibit gene transfection by electroporation in vivo

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