The development and characterization of a glutathione-sensitive cross-linked polyethylenimine gene vector

Wang, Youxiang; Chen, Ping; Shen, Jiacong

doi:10.1016/j.biomaterials.2006.05.049

Cited by 105 publications

(75 citation statements)

References 30 publications

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“…In particular, polyplexes capable of responding to environmental changes or stimuli by altering their properties and behavior seem to promise a significant improvement of the efficacy of the delivery process [3]. One of the several stimuli, which has been utilized for improving the efficiency of nucleic acid delivery, is the redox potential gradient existing between extracellular and intracellular environments [4][5][6][7][8][9][10]. The existence of such redox potential gradient has been exploited by incorporating disulfide bonds into the structure of the delivery vectors to provide them with the capability to release the therapeutic nucleic acids selectively in the subcellular reducing space [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Bcl-2 as a proxy redox stimulus to enhance activity of non-viral redox-responsive delivery vectors

et al. 2008

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Redox-sensitive non-viral delivery systems exploit intracellular reducing environment to improve the efficacy of the delivery of nucleic acids by selectively releasing the cargo in the subcellular space. Bcl-2 overexpression is frequently observed in human cancers and is closely associated with increased resistance to chemotherapy and radiotherapy. One of the biochemical alterations accompanying Bcl-2 overexpression is the increase in cellular glutathione (GSH) levels. In this study, we hypothesize that such increase of GSH concentrations will selectively enhance the transfection activity of redox-sensitive delivery systems in cells overexpressing Bcl-2. Transfection studies were conducted in MCF-7 mammary carcinoma cells and MCF-7 clones overexpressing Bcl-2. It was confirmed that Bcl-2 overexpression resulted in the expected increase in GSH concentrations. Redoxsensitive complexes containing plasmid DNA, mRNA, antisense oligodeoxynucleotides, and siRNA exhibited selectively increased activity in cells overexpressing Bcl-2 compared to non-redox complexes. The effect of Bcl-2 overexpression on the selective enhancement of transfection was highly dependent on the type of the delivered nucleic acid, and was most pronounced for mRNA. This study shows that Bcl-2 overexpression can serve as a proxy redox stimulus to enhance the activity of all major classes of potential nucleic acid therapeutics, when delivered using redoxsensitive vectors.

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Section: Introductionmentioning

confidence: 99%

Overexpression of Bcl-2 as a proxy redox stimulus to enhance activity of non-viral redox-responsive delivery vectors

et al. 2008

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“…Low molecular weight PEIs(such as 1.8-kDa PEI) have much lower cytotoxicity, but they cannot effectively condense DNA and display very poor gene transfection activity [33,34]. In order to reduce the cytotoxicity and enhance carrier unpacking into the cytosol and/or nucleus, intracellular-cleavable disulfide-linked PEIs have been designed for gene delivery [35][36][37][38][39]. The disulfide linkage is stable during blood circulation [40].…”

Section: Introductionmentioning

confidence: 99%

Efficient RNA delivery by integrin-targeted glutathione responsive polyethyleneimine capped gold nanorods

et al. 2015

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Guo, S., Efficient RNA delivery by integrin-targeted glutathione responsive polyethyleneimine capped gold nanorods, Acta Biomaterialia (2015), doi: http://dx.doi.org/10.1016/j.actbio. 2015.05.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. targeting, intracellular glutathione-triggered "off-on" release and endosomal escape, the RDG nanocarrier developed herein appears to be a highly promising non-viral vector for efficient RNAi.

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“…The strategy of preparing HMW polycations from low-molecular weight (LMW) oligocations via biodegradable linkages has been proven to reduce toxicity while retaining the gene transfer ability of the polyplexes. Up to now, several examples had been reported (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Hydrolysable PEIs were developed by cross-linking oligoethylenimine 800 Da (OEI) with ester bond bearing monomers or polyesters (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…Hydrolysable PEIs were developed by cross-linking oligoethylenimine 800 Da (OEI) with ester bond bearing monomers or polyesters (6)(7)(8)(9)(10)(11)(12). Biocleavable PEIs were prepared by thiolation of LMW PEI (13,14) or by cross-linking of OEI with disulfide bond containing linkers, including dimethyl 3, 3′-dithiobis(propionimidate) and dithiobis (succinimidyl propionate) (6,15,16). Bioreducible copolymers from N,N′-cystamine bisacrylamide (CBA) linker and different primary amines or oligoamines were explored too (17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Influence of the Molecular Weight of Bioreducible Oligoethylenimine Conjugates on the Polyplex Transfection Properties

Ruß

Wagner

2009

AAPS J

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Abstract. The purpose of the present study was to investigate the influence of molecular weights on the chemical, biophysical, and biological properties of bioreducible oligoethylenimine conjugates. The cationic conjugates were synthesized by polyaddition between branched oligoethylenimine 800 Da (OEI) and the disulfide bond containing N,N′-cystamine bisacrylamide (CBA) linker. A correlation between the copolymer molecular weights and the polyplex transfection properties was found. The OEI-CBA copolymers differing in molecular weights (from 8.6 to 37 kDa) showed good plasmid DNA binding ability resulting in compact 90-to 150-nm-sized polyplexes. Colloidal stability of the polyplexes was lost in reductive environment. A low concentration of dithiothreitol of 5 µM was sufficient to render polyplexes unstable in size. Reducing conditions at physiological salt concentration triggered polyplex dissociation. The bioreducible polymers displayed much lower cytotoxicity (IC 50 ∼100 μg/mL in cell culture) than branched polyethylenimine 25 kDa (BPEI) and linear polyethylenimine 22 kDa (LPEI). Reporter gene transfection experiments were done with CHO-K1 and B16-F10 cells. The largest (37 kDa) copolymer HC-6-8 demonstrated highest transfection levels among all the bioreducible copolymers, which was comparable with LPEI and much more effective than BPEI.

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The development and characterization of a glutathione-sensitive cross-linked polyethylenimine gene vector

Cited by 105 publications

References 30 publications

Overexpression of Bcl-2 as a proxy redox stimulus to enhance activity of non-viral redox-responsive delivery vectors

Overexpression of Bcl-2 as a proxy redox stimulus to enhance activity of non-viral redox-responsive delivery vectors

Efficient RNA delivery by integrin-targeted glutathione responsive polyethyleneimine capped gold nanorods

Influence of the Molecular Weight of Bioreducible Oligoethylenimine Conjugates on the Polyplex Transfection Properties

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