Hypoxia-inducible VEGF gene delivery to ischemic myocardium using water-soluble lipopolymer

Lee, Myoungkyu; Rentz, Jeffrey J; Bikram, Malavosklish; Han, Seonggyun; Bull, David A.; Kim, S W

doi:10.1038/sj.gt.3302034

Cited by 100 publications

(67 citation statements)

References 22 publications

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“…Previous work in our lab using water soluble lipopolymer (WSLP) produced significantly higher gene expression than naked pDNA and bPEI/pDNA in the same model [36]. WSLP also mediated higher transgene expression in ischemic rabbit myocardium as apposed to healthy myocardium using the hypoxia inducible pEpo-SV-VEGF plasmid [23]. We used WSLP as the positive control for our in vivo experiments.…”

Section: In Vivo Delivery Of Ss-paed/rtp-vegf In Ischemic Myocardiummentioning

confidence: 99%

“…Regulated VEFG expression was measured by using a hypoxia inducible RTP-VEGF plasmid as previously described [23] on H9C2 and A7R5 cells. Cells were plated in 6-well plates at 1.2 × 10 5 cells per well for H9C2 and in 12-well plates at 1.0 × 10 5 cells per well for A7R5 24 hr prior to transfection.…”

Section: Vegf Expression Under Normoxia and Hypoxiamentioning

confidence: 99%

“…Previous work in our lab was performed by injecting 200 μg pDNA complexed with WSLP into rabbit myocardium [23,36]. We initially decided to perform dose response injections with our SS-PAED/RTP-VEGF system starting at 100 μg RTP-VEGF and then increasing the dose until VEGF expression was apparent.…”

Section: In Vivo Delivery Of Ss-paed/rtp-vegf In Ischemic Myocardiummentioning

confidence: 99%

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

Christensen

Chang

Yockman

et al. 2007

Journal of Controlled Release

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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.

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Section: In Vivo Delivery Of Ss-paed/rtp-vegf In Ischemic Myocardiummentioning

confidence: 99%

Section: Vegf Expression Under Normoxia and Hypoxiamentioning

confidence: 99%

Section: In Vivo Delivery Of Ss-paed/rtp-vegf In Ischemic Myocardiummentioning

confidence: 99%

See 1 more Smart Citation

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

Christensen

Chang

Yockman

et al. 2007

Journal of Controlled Release

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“…44,45 The WSLP gene carrier forms self-assembling lipopolymer/DNA complexes with the therapeutic gene. The multifunctional characteristics of these novel polymers include DNA condensation, protection of DNA integrity, cell membrane adhesion and endosomal disruption capabilities with minimal toxicity.…”

Section: Ischemia-inducible Gene Therapy Jw Yockman Et Almentioning

confidence: 99%

“…12,44,45 In vitro analysis H9c2 and A7R5 cells were grown in 24-well plates with 500 ml complete media (DMEM+10% FBS). At 50% In vitro viability under hypoxia was accomplished by transfecting H9c2 or A7R5 cells with 1 mg of WSLP/ pRTP801-VEGF at similar N/P ratios as described above.…”

Section: Polymer Synthesismentioning

confidence: 99%

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

et al. 2008

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Interaction between the fluorinated amphiphilic copolymer poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate)‐graft‐poly(SPEG) and DNA

Xiong

Wang

et al. 2010

J of Applied Polymer Sci

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A synthesized copolymer, synthesized from HFMA (hexaflurobutyl methacrylate) and SPEG (PHFMA-g-PSPEG), was synthesized. PHFMA-g-PSPEG intercalated to the DNA base pair via a strong hydrophobic force, and this was conformed by ultraviolet spectroscopy, transmittance measurements, micropolarity measurements, resonance light scattering (RLS) spectroscopy, and particle size measurements. The copolymer was used as a new probe to detect DNA according to the RLS technique. The hydrophobic interaction between PHFMAg-PSPEG and DNA significantly enhanced the RLS signal, and the enhanced RLS intensity at 422 nm was proportional to the nucleic acid concentration within the range of 0.09-0.90 mg/L with a detection limit (3r) of 4.0 lg/L.

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Hypoxia-inducible VEGF gene delivery to ischemic myocardium using water-soluble lipopolymer

Cited by 100 publications

References 22 publications

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

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

Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct

Interaction between the fluorinated amphiphilic copolymer poly(2,2,3,4,4,4‐hexafluorobutyl methacrylate)‐graft‐poly(SPEG) and DNA

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