Cationic Liposome–Nucleic Acid Complexes for Gene Delivery and Silencing: Pathways and Mechanisms for Plasmid DNA and siRNA

Ewert, Kai K.; Zidovska, Alexandra; Ahmad, Ayesha; Bouxsein, Nathan F.; Evans, Heather M.; McAllister, Christopher S.; Samuel, Charles E.; Safinya, Cyrus R.

doi:10.1007/128_2010_70

Cited by 144 publications

(139 citation statements)

References 93 publications

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“…Although many successful preclinical studies have been reviewed using rodents as the models for testing lipid-based siRNA delivery (Wu and Nandamuri 2004;Ewert et al 2010;Schroeder et al 2010), there are very few reports of preclinical research conducted in NHPs. The successful applications of LNP-siRNA delivery in NHPs will pave the road to human clinical trials.…”

Section: Sirna Delivery Tested In Nhpsmentioning

confidence: 99%

Technologies for Investigating the Physiological Barriers to Efficient Lipid Nanoparticle–siRNA Delivery

Shu¹,

Abrams²

2013

J Histochem Cytochem.

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Small interfering RNA (siRNA) therapeutics have advanced from bench to clinical trials in recent years, along with new tools developed to enable detection of siRNA delivered at the organ, cell, and subcellular levels. Preclinical models of siRNA delivery have benefitted from methodologies such as stem-loop quantitative polymerase chain reaction, histological in situ immunofluorescent staining, endosomal escape assay, and RNA-induced silencing complex loading assay. These technologies have accelerated the detection and optimization of siRNA platforms to overcome the challenges associated with delivering therapeutic oligonucleotides to the cytosol of specific target cells. This review focuses on the methodologies and their application in the biodistribution of siRNA delivered by lipid nanoparticles.

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Section: Sirna Delivery Tested In Nhpsmentioning

confidence: 99%

Technologies for Investigating the Physiological Barriers to Efficient Lipid Nanoparticle–siRNA Delivery

Shu¹,

Abrams²

2013

J Histochem Cytochem.

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“…6,8 Cationic liposomes are a promising nonviral delivery system, and have been extensively studied for siRNA and plasmid DNA delivery. 9 The addition of polyethylene glycol (PEG) to the liposomes can decrease reticuloendothelial system recognition, thereby prolonging the circulation time in biological fluids. Although PEGylated liposomes provide a more stable preparation, the steric barrier of the grafted PEG moiety on the surface of the liposomes reduces interaction between the delivery system and the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells

Chen¹,

Lu²,

Yeh³

et al. 2011

IJN

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Background Human retinal pigment epithelial cells are promising target sites for small interfering RNA (siRNA) that might be used for the prevention and/or treatment of choroidal neovascularization by inhibiting the expression of angiogenic factor; for example, by downregulating expression of the vascular endothelial growth factor gene. Methods A novel functional lipid, DSPE-PEG-RGD, a Arg(R)-Gly(G)-Asp(D) motif peptide conjugated to 1, 2-distearoyl- sn -glycero-3-phosphoethanolamine- N-[maleimide (polyethylene glycol)-2000], was synthesized for the preparation of siRNA-loaded RGD-PEGylated liposomes to enhance uptake of encapsulated siRNA in retinal pigment epithelial cells. Various liposomes, with 1 mol% and 5 mol% PEGylated lipid or 1 mol% and 5 mol% RGD-PEGylated lipid, were fabricated. Results Characterization of the liposomes, including siRNA entrapment efficiency, average particle size and ζ-potential, were determined to be as follows: >96%, 129.7 ± 51 to 230.7 ± 60.7 nm, and 17.3 ± 0.6 to 32 ± 1.3 mV, respectively. For the in vitro retinal pigment epithelial cell studies, the RGD-PEGylated liposomes had high delivery efficiency with siRNA delivery, about a four-fold increase compared with the PEGylated liposomes. Comparison of the various liposomes showed that the 1 mol% RGD-modified liposome had less cytotoxicity and higher siRNA delivery efficiency than the other liposomes. The antibody blocking assay confirmed that uptake of the 1 mol% RGD-PEGylated liposome was via integrin receptor- mediated endocytosis in retinal pigment epithelial cells. Conclusion The results of this study suggest that RGD-PEGylated liposomes might be useful for siRNA delivery into retinal pigment epithelial cells by integrin receptor-medicated endocytosis.

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“…DOTAP is one of the most frequently used cationic lipids to prepare cationic liposomes. [25][26][27] The particle size and ζ-potential of cationic liposome/pDNA complexes (charge ratio at 1.0 : 2.3) used in this study were 516.8±18.5 nm and 53.1±3.8 mV, respectively ( Table 1). As shown in Fig.…”

Section: Effect Of Mechanical Agitation On Pdna Transfectionmentioning

confidence: 99%

Effect of Mechanical Agitation on Cationic Liposome Transport across an Unstirred Water Layer in Caco-2 Cells

Kono

Iwasaki

Matsuoka

et al. 2016

Biological & Pharmaceutical Bulletin

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To develop an effective oral delivery system for plasmid DNA (pDNA) using cationic liposomes, it is necessary to clarify the characteristics of uptake and transport of cationic liposome/pDNA complexes into the intestinal epithelium. In particular, evaluation of the involvement of an unstirred water layer (UWL), which is a considerable permeability barrier, in cationic liposome transport is very important. Here, we investigated the effects of a UWL on the transfection efficiency of cationic liposome/pDNA complexes into a Caco-2 cell monolayer. When Caco-2 cells were transfected with cationic liposome/pDNA complexes in shaking cultures to reduce the thickness of the UWL, gene expression was significantly higher in Caco-2 cells compared with static cultures. We also found that this enhancement of gene expression by shaking was not attributable to activation of transcription factors such as activator protein-1 and nuclear factor-kappaB (NF-κB). In addition, the increase in gene expression by mechanical agitation was observed at all charge ratios (1.5, 2.3, 3.1, 4.5) of cationic liposome/pDNA complexes. Transport experiments using Transwells demonstrated that mechanical agitation increased the uptake of cationic liposome/pDNA complexes by Caco-2 cells, whereas transport of the complexes across a Caco-2 cell monolayer did not occurr. Moreover, the augmentation of the gene expression of cationic liposome/pDNA complexes by shaking was observed in Madin-Darby canine kidney cells. These results indicate that a UWL greatly affects the uptake and transfection efficiency of cationic liposome/pDNA complexes into an epithelial monolayer in vitro.

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Cationic Liposome–Nucleic Acid Complexes for Gene Delivery and Silencing: Pathways and Mechanisms for Plasmid DNA and siRNA

Cited by 144 publications

References 93 publications

Technologies for Investigating the Physiological Barriers to Efficient Lipid Nanoparticle–siRNA Delivery

Technologies for Investigating the Physiological Barriers to Efficient Lipid Nanoparticle–siRNA Delivery

Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells

Effect of Mechanical Agitation on Cationic Liposome Transport across an Unstirred Water Layer in Caco-2 Cells

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