Hybrid vector including polyethylenimine and cationic lipid, DOTMA, for gene delivery

Matsumoto, Megumi; Reiko, Kishikawa; Kurosaki, Tomoaki; Nakagawa, Hiroo; Ichikawa, Nobuhiro; Hamamoto, Tomoyuki; To, Hideto; Kitahara, Takashi; Sasaki, Hidetada

doi:10.1016/j.ijpharm.2008.07.010

Cited by 25 publications

(26 citation statements)

References 29 publications

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“…This indicates that the success of lipopolyplexes relies on a loosely condensed polyplex core modified by a moderate amount of lipid. Interestingly, earlier studies have also reported that the highest enhancement of transfection by PEI and DOTAP-Chol or DOTMA was achieved at relatively low PEI/DNA ratios of 4.5 23 and 2, 21 respectively, although the reason for this was unclear. It is possible that the relaxed polyplex core benefited transfection by achieving a balance between DNA protection and subsequent DNA liberation for gene expression.…”

Section: Discussionmentioning

confidence: 96%

“…This suggests that cationic lipids formed an outer coat around the preformed polyplexes, in agreement with the "core-shell" structure of lipopolyplexes proposed by earlier studies. 21,22 Nevertheless, it should be noted that the surface charge of lipopolyplexes also increased with increasing PEI/ DNA ratio. Thus, it is possible that the polyplex core was not entirely wrapped by the lipids, as shown in Scheme 1.…”

Section: Discussionmentioning

confidence: 99%

“…PEI/DNA polyplexes in combination with liposomes containing DOCSPER, 19 DOSPER, 19 DOTAP, 20 DOTMA, 21 DPPC, 22 or DPPG 22 have been shown to improve the transfection of immortal cell lines under serum conditions. Several parameters, in particular the lipid structure and vector/DNA molar ratio, were suggested to be factors influencing the transfection behavior of the lipopolyplexes.…”

Section: Introductionmentioning

confidence: 99%

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Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells

Song¹,

Wang²,

He³

et al. 2012

IJN

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Background: Effective gene transfection without serum deprivation is a prerequisite for successful stem cell-based gene therapy. Polyethylenimine (PEI) is an efficient nonviral gene vector, but its application has been hindered by serum sensitivity and severe cytotoxicity. Methods: To solve this problem, a new family of lipopolyplexes was developed by coating PEI/ DNA polyplexes with three serum-resistant cationic lipids, namely, lysinylated, histidylated, and arginylated cholesterol. The physical properties, transfection efficiency, cellular uptake, subcellular distribution, and cytotoxicity of the lipopolyplexes was investigated. Results: The outer coat composed of lysinylated or histidylated cholesterol remarkably improved the transfection efficiency of the polyplex with a low PEI/DNA ratio of 2 in the presence of serum. The resulting lysinylated and histidylated cholesterol lipopolyplexes were even more efficient than the best performing polyplex with a high PEI/DNA ratio of 10. Results from cellular uptake and subcellular distribution studies suggest that their higher transfection efficiency may result from accelerated DNA nuclear localization. The superiority of the lipopolyplexes over the best performing polyplex was also confirmed by delivering the therapeutic gene, hVEGF 165 . Equally importantly, the lipid coating removed the necessity of introducing excess free PEI chains into the transfection solution for higher efficiency, generating lipopolyplexes with no signs of cytotoxicity. Conclusion: Noncovalent modification of polyplexes with lysinylated and histidylated cholesterol lipids can simultaneously improve efficiency and reduce the toxicity of gene delivery under serum conditions, showing great promise for genetic modification of bone marrow stem cells.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells

Song¹,

Wang²,

He³

et al. 2012

IJN

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“…Previous studies by electron microscopy have been suggested that lipopolyplexes prepared by this method have viruslike structure. In this structure, the central core consists of polycation-DNA and lipid bilayers make its shell and also particle's surface properties to be determined by liposome [10,18,19].…”

Section: Discussionmentioning

confidence: 99%

“…Covalent and non-covalent modifications of liposomes have been evaluated in several studies for improved DNA and siRNA delivery [7][8][9][10][11][12][13][14][15]. It has been reported that a combination of low molecular (700 and 2000 Da) and high molecular weight (22 and 25 KDa) PEIs resulted in an improvement of transfection efficiency in vitro [7,11].…”

Section: Introductionmentioning

confidence: 99%

Liposome-linear polyethyleneimine-DNA Nanocomplexes for Gene Delivery: Preparation, Characterization and In Vitro Transfection Activity

Motaharinia¹,

Ramezani²,

Malaekeh-Nikouei

et al. 2011

CNANO

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The aim of the present study was to improve transfection efficiency using different combinations of cationic liposomes, linear polyethylenimine and DNA. A novel gene delivery system (lipopolyplex) was developed by premixing cationic liposomes containing cholesterol or oligoamine modified cholesterol (derivative I-III) and linear polyethyleneimines (PEIs) following addition of plasmid at three different C/P ratios. The resultant complexes were characterized for their size, zeta potential and ability of DNA condensation. Luciferase reporter gene was used for determination of transfection efficiency in Neuro2A cells. Mean particle size of prepared complexes was less than 200 nm and they showed positive surface charge. The transfection efficiency of vectors was reduced by increasing in carrier concentration/plasmid DNA ratio (C/P ratio) while gene expression of cationic liposome or PEI was increased at higher C/P ratios. Complexes composed of PEI 2.5 or 250 kDa and liposome containing derivative I had the highest transfection activity. Furthermore, non-viral vectors described in this study showed low cytotoxicity. The results show that small and large molecular weight linear PEI in combination with liposome have little toxicity and may enhance transfection efficiency.

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Development of targeted gene delivery system based on liposome and PAMAM dendrimer functionalized with hyaluronic acid and TAT peptide: In vitro and in vivo studies

Ebrahimian

Hashemi

Farzadnia

et al. 2022

Biotechnology Progress

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The development of gene delivery systems is essential to improve their transfection efficiency and cytotoxicity. Combination of lipid and polymeric nanoparticles with the characteristics of both systems have been considered as a next‐generation gene delivery platform. In the current study, we designed a novel and efficient targeted gene delivery system based on liposome and PAMAM dendrimer in cancer cells. Two polymeric formulations containing polyamidoamine‐TAT (PAMAM‐TAT) and PAMAM‐TAT‐Hyaluronic acid (HA) and two lipopolymeric carriers including PAMAM‐TAT‐Liposome and PAMAM‐TAT‐HA‐Liposome were complexed with the enhanced green fluorescent protein (EGFP) plasmid and then evaluated in terms of physicochemical characteristics. The cytotoxicity and transfection efficiency of these synthetized carriers were accomplished against murine colon carcinoma cell line (C26). The biodistribution of polyplexes and lipoployplexes was also evaluated in the C26 tumor bearing mice. The results showed no significant toxicity for all designed nanoparticles (NPs) in C/P4. The highest gene expression was observed using lipopolyplex PAMAM‐TAT‐HA‐Liposome in C/P4 (ratio polymer/DNA; wt/wt). Biodistribution study demonstrated more aggregation of targeted lipopolyplex in tumor cells than other nanoparticles (NPs). It could be concluded that the developed targeted lipopolymeric complex could serve as promising nanotherapeutic system for gene therapy.

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Hybrid vector including polyethylenimine and cationic lipid, DOTMA, for gene delivery

Cited by 25 publications

References 29 publications

Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells

Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells

Liposome-linear polyethyleneimine-DNA Nanocomplexes for Gene Delivery: Preparation, Characterization and In Vitro Transfection Activity

Development of targeted gene delivery system based on liposome and PAMAM dendrimer functionalized with hyaluronic acid and TAT peptide: In vitro and in vivo studies

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