| Intravenous transferrin, RGD peptide and dual-targeted nanoparticles enhance anti-VEGF intraceptor gene delivery to laser-induced CNV. | |
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MedLine Citation:
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PMID: 19194480 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Choroidal neovascularization (CNV) leads to loss of vision in age-related macular degeneration (AMD), the leading cause of blindness in adult population over 50 years old. In this study, we developed intravenously administered, nanoparticulate, targeted nonviral retinal gene delivery systems for the management of CNV. CNV was induced in Brown Norway rats using a 532 nm laser. We engineered transferrin, arginine-glycine-aspartic acid (RGD) peptide or dual-functionalized poly-(lactide-co-glycolide) nanoparticles to target delivery of anti-vascular endothelial growth factor (VEGF) intraceptor plasmid to CNV lesions. Anti-VEGF intraceptor is the only intracellularly acting VEGF inhibitory modality. The results of the study show that nanoparticles allow targeted delivery to the neovascular eye but not the control eye on intravenous administration. Functionalizing the nanoparticle surface with transferrin, a linear RGD peptide or both increased the retinal delivery of nanoparticles and subsequently the intraceptor gene expression in retinal vascular endothelial cells, photoreceptor outer segments and retinal pigment epithelial cells when compared to nonfunctionalized nanoparticles. Most significantly, the CNV areas were significantly smaller in rats treated with functionalized nanoparticles as compared to the ones treated with vehicle or nonfunctionalized nanoparticles. Thus, surface-functionalized nanoparticles allow targeted gene delivery to the neovascular eye on intravenous administration and inhibit the progression of laser-induced CNV in a rodent model. |
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Authors:
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S R Singh; H E Grossniklaus; S J Kang; H F Edelhauser; B K Ambati; U B Kompella |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-02-05 |
Journal Detail:
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Title: Gene therapy Volume: 16 ISSN: 1476-5462 ISO Abbreviation: Gene Ther. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-14 Completed Date: 2010-05-12 Revised Date: 2011-12-07 |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: England |
Other Details:
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Languages: eng Pagination: 645-59 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chemistry, Physical Choroidal Neovascularization / etiology, pathology, therapy* Disease Models, Animal Gene Therapy / methods* Gene Transfer Techniques* Injections, Intravenous Lasers Male Microscopy, Confocal Nanoparticles / administration & dosage*, chemistry Oligopeptides / pharmacology Rats Rats, Inbred BN Receptors, Vascular Endothelial Growth Factor / genetics* Retina / metabolism Retinal Pigment Epithelium / metabolism Tissue Distribution Transferrin / pharmacology Vascular Endothelial Growth Factor A / antagonists & inhibitors*, genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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5R01EY017182/EY/NEI NIH HHS; P30 EY006360-25/EY/NEI NIH HHS; R21 EY017360/EY/NEI NIH HHS; R21 EY017360-02/EY/NEI NIH HHS; R24 EY017045/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Oligopeptides; 0/Transferrin; 0/Vascular Endothelial Growth Factor A; 99896-85-2/arginyl-glycyl-aspartic acid; EC 2.7.10.1/Receptors, Vascular Endothelial Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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