Triggered intracellular activation of disulfide crosslinked polyelectrolyte gene delivery complexes with extended systemic circulation in vivo

Oupický, David; Carlisle, Robert; Seymour, Len

doi:10.1038/sj.gt.3301446

Cited by 143 publications

(164 citation statements)

References 18 publications

(27 reference statements)

Supporting

Mentioning

161

Contrasting

Order By: Relevance

“…Lower gene expression at higher BSO concentrations suggests the inability of SS-PAED/pDNA complexes to completely dissociate therefore creating an extra rate limiting step in nuclear localization of transfected pDNA. This rate limiting step was suggested in our previous work using confocal microscopy as well as work published by other groups [21,[28][29][30]. It should also be noted that the decline in gene expression for SS-PAED mediated delivery should not be associated with toxicity since bPEI mediated delivery revealed no significant change in gene expression over the range of BSO used.…”

Section: Ss-paed Mediated Gene Delivery Is Dependent On Glutathionesupporting

confidence: 66%

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

Christensen

Chang

Yockman

et al. 2007

Journal of Controlled Release

View full text Add to dashboard Cite

Delivery of the hypoxia inducible vascular endothelial growth factor (RTP-VEGF) plasmid using a novel reducible disulfide poly(amido ethylenediamine) (SS-PAED) polymer carrier was studied in vitro and in vivo. In vitro transfection of primary rat cardiomyoblasts (H9C2) showed SS-PAED at a weighted ratio of 12:1 (polymer/DNA) mediates 16 fold higher expression of luciferase compared to an optimized bPEI control. FACS analysis revealed up to 57 ± 2% GFP positive H9C2s. The efficiency of plasmid delivery to H9C2 using SS-PAED was found to depend upon glutathione (GSH) levels inside the cell. SS-PAED mediated delivery of RTP-VEGF plasmid produced significantly higher levels of VEGF expression (up to 76 fold) under hypoxic conditions compared to normoxic conditions in both H9C2 and rat aortic smooth muscle cells (A7R5). Using SS-PAED, delivery of RTP-VEGF was investigated in a rabbit myocardial infarct model using 100 μg RTP-VEGF. Results showed up to 4 fold increase in VEGF protein expression in the region of the infarct compared to injections of SS-PAED/RTP-Luc. In conclusion, SS-PAED mediated therapeutic delivery improves the efficacy of ischemia-inducible VEGF gene therapy both in vitro and in vivo and therefore, has potential for the promotion of neo-vascular formation and improvement of tissue function in ischemic myocardium.

show abstract

Section: Ss-paed Mediated Gene Delivery Is Dependent On Glutathionesupporting

confidence: 66%

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

Christensen

Chang

Yockman

et al. 2007

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…While polymers have been previously engineered for the controlled release of nucleic acids (35)(36)(37)(38)(39), the release has largely relied on cellular process. In this report, we have demonstrated the synthesis and functionality of a compound, B-PC-PEI, that is able to selectively release nucleic acids from a solid support after light application, and which has many potential applications ranging from biological studies to therapeutic applications.…”

Section: Discussionmentioning

confidence: 99%

Biotinylated Photocleavable Polyethylenimine: Capture and Triggered Release of Nucleic Acids from Solid Supports

Handwerger

Diamond

2007

Bioconjugate Chem.

View full text Add to dashboard Cite

A biotinylated photocleavable polyethylenimine (B-PC-PEI) was designed and synthesized for the capture and controlled release of nucleic acids from solid supports. B-PC-PEI was synthesized via a 3-step reaction process and verified by 1 H NMR and mass spectrometry. In aqueous solution, the o-nitrobenzyl group within B-PC-PEI was efficiently cleaved by 5 min of 365 nm light exposure from a distance of 20 cm (9 mW/cm 2 ). When coupled to streptavidin-coated beads, the PEI domain of Cy5-labeled B-PC-PEI was released by 365 nm light exposure. In contrast, a Cy5-labeled biotinylated PEI (B-PEI) was used as a control and negligible fluorescence loss was observed. Cy5-labeled siRNA was electrostatically captured to streptavidin-coated beads preabsorbed with B-PC-PEI or B-PEI, and flow cytometry demonstrated significant loss of fluorescence from the bead surface after 5 min of light exposure only for B-PC-PEI, demonstrating controlled release of siRNA from the bead surface. Finally, the release of the Cy5-labeled siRNA into the supernatant was quantified. The release of Cy5-siRNA into the supernatant was significantly greater after 5 min of light exposure for B-PC-PEI/streptavidin beads compared to 0 min exposure and remained unchanged for B-PEI/streptavidin beads. B-PC-PEI facilitates capture and triggered release of surface-tethered nucleic acids with light exposure and is fully compatible with streptavidin-based applications.

show abstract

“…Although the hemolytic activity was reduced by this modification, it seemed to still be enough for endosomal release and carrier disassembly in the reductive environment of the cytosol. [127] The modification of the e-amino groups of pLL with 3-(2-aminoethyldithio)propionyl residues [144] or their crosslinking with DTBP [145] comprises another approach utilizing reductively degradable gene carriers. These molecules were able to complex nucleotides into particles that were stable under physiological conditions but disintegrated upon treatment with GSH.…”

Section: Disulfides For the Stabilization Of The Carriermentioning

confidence: 99%

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

Triggered intracellular activation of disulfide crosslinked polyelectrolyte gene delivery complexes with extended systemic circulation in vivo

Cited by 143 publications

References 18 publications

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

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

Biotinylated Photocleavable Polyethylenimine: Capture and Triggered Release of Nucleic Acids from Solid Supports

Delivery of Nucleic Acids via Disulfide‐Based Carrier Systems

Contact Info

Product

Resources

About