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dc.contributor.authorSalehi-Had, Hani
dc.contributor.authorRoh, Mi In
dc.contributor.authorGiani, Andrea
dc.contributor.authorHisatomi, Toshio
dc.contributor.authorNakao, Shintaro
dc.contributor.authorKim, Ivana Kyung
dc.contributor.authorGragoudas, Evangelos Stelios
dc.contributor.authorVavvas, Demetrios
dc.contributor.authorGuccione, Samira
dc.contributor.authorMiller, Joan Whitten
dc.date.accessioned2011-09-13T17:56:32Z
dc.date.issued2011
dc.identifier.citationSalehi-Had, Hani, Mi In Roh, Andrea Giani, Toshio Hisatomi, Shintaro Nakao, Ivana K. Kim, Evangelos S. Gragoudas, Demetrios Vavvas, Samira Guccione, and Joan W. Miller. 2011. Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. PLoS ONE 6(4): e18864.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5130451
dc.description.abstractPurpose: The integrin αvβ3 is differentially expressed on neovascular endothelial cells. We investigated whether a novel intravenously injectable αvβ3 integrin-ligand coupled nanoparticle (NP) can target choroidal neovascular membranes (CNV) for imaging and targeted gene therapy. Methods: CNV lesions were induced in rats using laser photocoagulation. The utility of NP for in vivo imaging and gene delivery was evaluated by coupling the NP with a green fluorescing protein plasmid (NP-GFPg). Rhodamine labeling (Rd-NP) was used to localize NP in choroidal flatmounts. Rd-NP-GFPg particles were injected intravenously on weeks 1, 2, or 3. In the treatment arm, rats received NP containing a dominant negative Raf mutant gene (NP-ATPμ-Raf) on days 1, 3, and 5. The change in CNV size and leakage, and TUNEL positive cells were quantified. Results: GFP plasmid expression was seen in vivo up to 3 days after injection of Rd-NP-GFPg. Choroidal flatmounts confirmed the localization of the NP and the expression of GFP plasmid in the CNV. Treating the CNV with NP-ATPμ-Raf decreased the CNV size by 42% (P<0.001). OCT analysis revealed that the reduction of CNV size started on day 5 and reached statistical significance by day 7. Fluorescein angiography grading showed significantly less leakage in the treated CNV (P<0.001). There were significantly more apoptotic (TUNEL-positive) nuclei in the treated CNV. Conclusion: Systemic administration of αvβ3 targeted NP can be used to label the abnormal blood vessels of CNV for imaging. Targeted gene delivery with NP-ATPμ-Raf leads to a reduction in size and leakage of the CNV by induction of apoptosis in the CNV.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi://10.1371/journal.pone.0018864en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084713/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectbiotechnologyen_US
dc.subjectbionanotechnologyen_US
dc.subjectmedicineen_US
dc.subjectopthalmologyen_US
dc.subjectmacular disordersen_US
dc.subjectretinal disordersen_US
dc.titleUtilizing Targeted Gene Therapy with Nanoparticles Binding Alpha v Beta 3 for Imaging and Treating Choroidal Neovascularizationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorMiller, Joan Whitten
dc.date.available2011-09-13T17:56:32Z
dash.affiliation.otherHMS^Ophthalmologyen_US
dash.affiliation.otherHMS^Ophthalmologyen_US
dc.identifier.doi10.1371/journal.pone.0018864*
dash.contributor.affiliatedRoh, Mi In
dash.contributor.affiliatedGragoudas, Evangelos
dash.contributor.affiliatedKim, Ivana
dash.contributor.affiliatedMiller, Joan
dash.contributor.affiliatedVavvas, Demetrios


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