Reducible poly(amido ethylenediamine) for hypoxia-inducible VEGF delivery

Christensen, Lane V.; Chang, Chia-Wei; Yockman, James W.; Conners, Rafe; Jackson, Heidi H.; Zhong, Zhiyuan; Feijén, Jan; Bull, David A.; Kim, Sung Wan

doi:10.1016/j.jconrel.2006.12.018

Cited by 64 publications

(52 citation statements)

References 38 publications

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“…Reasons for the failure to reverse the changes in cellular redox state induced by Bcl-2 expression are currently unknown. Most published studies that investigated the role of GSH in the activity of redox complexes used BSO, which specifically inhibits GSH biosynthesis in the cytoplasm [6,12,22,23]. Typically, a small decrease in the transfection activity of pDNA complexes was reported.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…It is reasonable to hypothesize that changes in intracellular GSH concentrations will alter activity of redox polyplexes. Indeed, available evidence suggests that artificially changing cellular GSH levels leads to changes in biological activity of polyplexes [6,12,22,23]. Modulation of GSH levels using either buthionine sulfoximine (BSO), an inhibitor of cytosolic GSH synthesis or enhancement of GSH levels using GSH monoethyl ester (GSH-Et) demonstrated a small, but significant effect on the transfection activity of plasmid DNA (pDNA) complexes.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Although the delivery of nucleic acids in the field of TE is quite auspicious, this approach still remains in its experimental phases, [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] and only a very limited number of studies applies carriers that rely on the described redox potential gradient. [55,56] This review will focus on the redox-potential trigger between the extra-and intracellular environments. Furthermore, the basic synthetic approaches for introducing disulfide bonds into molecules will be described.…”

Section: Reviewmentioning

confidence: 99%

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

et al. 2009

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Nucleic acids are not only expected to assume a pivotal position as "drugs" in the treatment of genetic and acquired diseases, but could also act as molecular cues to control the microenvironment during tissue regeneration. Despite this promise, the efficient delivery of nucleic acids to their side of action is still the major hurdle. One among many prerequisites for a successful carrier system for nucleic acids is high stability in the extracellular environment, accompanied by an efficient release of the cargo in the intracellular compartment. A promising strategy to create such an interactive delivery system is to exploit the redox gradient between the extra- and intracellular compartments. In this review, emphasis is placed on the biological rationale for the synthesis of redox sensitive, disulfide-based carrier systems, as well as the extra- and intracellular processing of macromolecules containing disulfide bonds. Moreover, the basic synthetic approaches for introducing disulfide bonds into carrier molecules, together with examples that demonstrate the benefit of disulfides at the individual stages of nucleic acid delivery, will be presented.

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“…The results indicated that both polymers encapsulated pSilencer 4.1-CMV FANCF shRNA well and were suitable for gene delivery. 29 Furthermore, the higher encapsulation efficiency of Agm-CBA compared to Arg-CBA might have been due to the carboxyl group in Arg, which influenced the charge density of Arg-CBA. From our results, it seemed that the positive-charge density of the polymer played an important role in encapsulation.…”

Section: Encapsulation Efficiency Of Polymeric Carriersmentioning

confidence: 99%