Bisphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents
The clinical use of metallic expandable intravascular stents has resulted in improved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector de...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2006-01, Vol.103 (1), p.159-164 |
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| creator | Fishbein, Ilia Alferiev, Ivan S. Nyanguile, Origene Gaster, Richard Vohs, John M. Wong, Gordon S. Felderman, Howard Chen, I-Wei Choi, Hoon Wilensky, Robert L. Levy, Robert J. |
| description | The clinical use of metallic expandable intravascular stents has resulted in improved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-bisphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine bisphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular bisphosphonate layer on metal alloy surfaces (steel, nitinol, and cobaltchromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Adinducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 ± 0.27 and 3.4 ± 0.35; Ad-iNOS vs. control, P < 0.01). It is concluded that effective gene vector delivery from metallic stent surfaces can be achieved by using this approach. |
| doi_str_mv | 10.1073/pnas.0502945102 |
| format | Article |
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However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-bisphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine bisphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular bisphosphonate layer on metal alloy surfaces (steel, nitinol, and cobaltchromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Adinducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 ± 0.27 and 3.4 ± 0.35; Ad-iNOS vs. control, P < 0.01). It is concluded that effective gene vector delivery from metallic stent surfaces can be achieved by using this approach.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0502945102</identifier><identifier>PMID: 16371477</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adenoviridae - metabolism ; Alloys ; Angioplasty ; Angioplasty - methods ; Animals ; Antibodies ; Arteries ; Biological Sciences ; Blood vessels ; Cardiovascular disease ; Cells, Cultured ; Coronary Artery Disease - complications ; Coronary Artery Disease - surgery ; Diphosphonates ; Diphosphonates - metabolism ; Gene therapy ; Genes, Reporter - genetics ; Genetic Therapy - methods ; Genetic vectors ; Genetic Vectors - metabolism ; Genetic Vectors - therapeutic use ; Graft Occlusion, Vascular - etiology ; Graft Occlusion, Vascular - therapy ; Green Fluorescent Proteins - metabolism ; Male ; Medical treatment ; Metal surfaces ; Metals ; Nitric Oxide Synthase Type II - metabolism ; Polyamines - metabolism ; Rats ; Rats, Sprague-Dawley ; Spectrum Analysis ; Steels ; Stents ; Transduction, Genetic - methods</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2006-01, Vol.103 (1), p.159-164</ispartof><rights>Copyright 2006 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jan 3, 2006</rights><rights>Copyright © 2006, The National Academy of Sciences 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4392-32c5db8bfd46d73860a17604cd74e0c87fcea2095473ee2ff821f53160db2c0a3</citedby><cites>FETCH-LOGICAL-c4392-32c5db8bfd46d73860a17604cd74e0c87fcea2095473ee2ff821f53160db2c0a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/103/1.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30048268$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30048268$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27923,27924,53790,53792,58016,58249</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16371477$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fishbein, Ilia</creatorcontrib><creatorcontrib>Alferiev, Ivan S.</creatorcontrib><creatorcontrib>Nyanguile, Origene</creatorcontrib><creatorcontrib>Gaster, Richard</creatorcontrib><creatorcontrib>Vohs, John M.</creatorcontrib><creatorcontrib>Wong, Gordon S.</creatorcontrib><creatorcontrib>Felderman, Howard</creatorcontrib><creatorcontrib>Chen, I-Wei</creatorcontrib><creatorcontrib>Choi, Hoon</creatorcontrib><creatorcontrib>Wilensky, Robert L.</creatorcontrib><creatorcontrib>Levy, Robert J.</creatorcontrib><title>Bisphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The clinical use of metallic expandable intravascular stents has resulted in improved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-bisphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine bisphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular bisphosphonate layer on metal alloy surfaces (steel, nitinol, and cobaltchromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Adinducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 ± 0.27 and 3.4 ± 0.35; Ad-iNOS vs. control, P < 0.01). It is concluded that effective gene vector delivery from metallic stent surfaces can be achieved by using this approach.</description><subject>Adenoviridae - metabolism</subject><subject>Alloys</subject><subject>Angioplasty</subject><subject>Angioplasty - methods</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Arteries</subject><subject>Biological Sciences</subject><subject>Blood vessels</subject><subject>Cardiovascular disease</subject><subject>Cells, Cultured</subject><subject>Coronary Artery Disease - complications</subject><subject>Coronary Artery Disease - surgery</subject><subject>Diphosphonates</subject><subject>Diphosphonates - metabolism</subject><subject>Gene therapy</subject><subject>Genes, Reporter - genetics</subject><subject>Genetic Therapy - methods</subject><subject>Genetic vectors</subject><subject>Genetic Vectors - metabolism</subject><subject>Genetic Vectors - therapeutic use</subject><subject>Graft Occlusion, Vascular - etiology</subject><subject>Graft Occlusion, Vascular - therapy</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Metal surfaces</subject><subject>Metals</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Polyamines - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spectrum Analysis</subject><subject>Steels</subject><subject>Stents</subject><subject>Transduction, Genetic - methods</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1vFDEQxS1ERI5ATQVaUaTbZPyx9rpBggQSpIQUCbSWzzvm9rS3vtjeiPz3-JRTLlBAMZpifvPm2Y-QNxSOKCh-vB5tOoIGmBYNBfaMzChoWkuh4TmZATBVt4KJffIypSUA6KaFF2SfSq6oUGpGvn3q03oRNjXajPUldn3pXXWGI1Y_0OUQq1Mc-juM95WPYVXlBVaXmO1QXU_RW4epCr66zjjm9IrseTskfL3tB-T7l883J-f1xdXZ15OPF7UTXLOaM9d083buOyE7xVsJlioJwnVKILhWeYeWFbdCcUTmfcuobziV0M2ZA8sPyIcH3fU0X2Hnyu1oB7OO_crGexNsb_6cjP3C_Ax3hnKqWqWKwOFWIIbbCVM2qz45HAY7YpiSUSAbCbz5L0iVkJwLVsD3f4HLMMWx_IJhQLnmmuoCHT9ALoaUIvpHyxTMJlGzSdTsEi0b756-dMdvI3xicLO5k-OGGtpo46dhyPgrF_Dtv8DdfJlK6I8ABxAtky3_DWiwvU0</recordid><startdate>20060103</startdate><enddate>20060103</enddate><creator>Fishbein, Ilia</creator><creator>Alferiev, Ivan S.</creator><creator>Nyanguile, Origene</creator><creator>Gaster, Richard</creator><creator>Vohs, John M.</creator><creator>Wong, Gordon S.</creator><creator>Felderman, Howard</creator><creator>Chen, I-Wei</creator><creator>Choi, Hoon</creator><creator>Wilensky, Robert L.</creator><creator>Levy, Robert J.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060103</creationdate><title>Bisphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents</title><author>Fishbein, Ilia ; 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However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-bisphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine bisphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular bisphosphonate layer on metal alloy surfaces (steel, nitinol, and cobaltchromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Adinducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 ± 0.27 and 3.4 ± 0.35; Ad-iNOS vs. control, P < 0.01). It is concluded that effective gene vector delivery from metallic stent surfaces can be achieved by using this approach.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>16371477</pmid><doi>10.1073/pnas.0502945102</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoviridae - metabolism Alloys Angioplasty Angioplasty - methods Animals Antibodies Arteries Biological Sciences Blood vessels Cardiovascular disease Cells, Cultured Coronary Artery Disease - complications Coronary Artery Disease - surgery Diphosphonates Diphosphonates - metabolism Gene therapy Genes, Reporter - genetics Genetic Therapy - methods Genetic vectors Genetic Vectors - metabolism Genetic Vectors - therapeutic use Graft Occlusion, Vascular - etiology Graft Occlusion, Vascular - therapy Green Fluorescent Proteins - metabolism Male Medical treatment Metal surfaces Metals Nitric Oxide Synthase Type II - metabolism Polyamines - metabolism Rats Rats, Sprague-Dawley Spectrum Analysis Steels Stents Transduction, Genetic - methods |
| title | Bisphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents |
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