Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization.
<h4>Purpose</h4>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.&...
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Public Library of Science (PLoS)
2011
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oai:doaj.org-article:db5376c1ba134f518bf531780f67858b2021-11-18T06:54:36ZUtilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization.1932-620310.1371/journal.pone.0018864https://doaj.org/article/db5376c1ba134f518bf531780f67858b2011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21559527/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Hani Salehi-HadMi In RohAndrea GianiToshio HisatomiShintaro NakaoIvana K KimEvangelos S GragoudasDemetrios VavvasSamira GuccioneJoan W MillerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18864 (2011) |
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Medicine R Science Q |
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Medicine R Science Q Hani Salehi-Had Mi In Roh Andrea Giani Toshio Hisatomi Shintaro Nakao Ivana K Kim Evangelos S Gragoudas Demetrios Vavvas Samira Guccione Joan W Miller Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. |
| description |
<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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. |
| format |
article |
| author |
Hani Salehi-Had Mi In Roh Andrea Giani Toshio Hisatomi Shintaro Nakao Ivana K Kim Evangelos S Gragoudas Demetrios Vavvas Samira Guccione Joan W Miller |
| author_facet |
Hani Salehi-Had Mi In Roh Andrea Giani Toshio Hisatomi Shintaro Nakao Ivana K Kim Evangelos S Gragoudas Demetrios Vavvas Samira Guccione Joan W Miller |
| author_sort |
Hani Salehi-Had |
| title |
Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. |
| title_short |
Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. |
| title_full |
Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. |
| title_fullStr |
Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. |
| title_full_unstemmed |
Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. |
| title_sort |
utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/db5376c1ba134f518bf531780f67858b |
| work_keys_str_mv |
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