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Herein we present the development and biological evaluation of the integrin ligand <jats:italic>c<\/jats:italic>(RGDf(<jats:italic>N<\/jats:italic>Me)Nal) as a potent anti\u2010proliferative molecule that targets coronary artery smooth muscle cells (CASMCs). This peptide showed an antagonistic activity for \u03b1v\u03b23 and \u03b1v\u03b25 in the low\u2010nanomolar range, and selectivity against the platelet receptor \u03b1IIb\u03b23. In vitro, it efficiently inhibited the proliferation of CASMCs, displaying higher potency than the anti\u2010tumor drug candidate cilengitide. This peptide was then loaded into a polymer\u2010free bare metal stent (BMS), and its release studied at different time points. Up to seven days of elution, the peptide\u2010coated stents retained high anti\u2010proliferative activity toward CASMCs. Finally, the peptide was examined in vivo in a polymer\u2010free DES system in a rabbit iliac artery model. After 28 days of implantation, histopathological analysis revealed that the peptide clearly decreased neointimal growth and improved vessel healing and re\u2010endothelialization compared with the FDA\u2010approved Cypher DES. Our study shows that this type of lipophilic integrin ligand, when eluted from a polymer\u2010free stent system, has the potential to successfully decrease in\u2010stent restenosis in the absence of delayed vascular healing.<\/jats:p>","DOI":"10.1002\/cmdc.201400078","type":"journal-article","created":{"date-parts":[[2014,4,6]],"date-time":"2014-04-06T18:47:18Z","timestamp":1396810038000},"page":"1413-1418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Integrin Ligand <i>c<\/i>(RGDf(<i>N<\/i>Me)Nal) Reduces Neointimal Hyperplasia in a Polymer\u2010Free Drug\u2010Eluting Stent System"],"prefix":"10.1002","volume":"9","author":[{"given":"Florian","family":"Rechenmacher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Steigerwald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkhardt","family":"Laufer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias G.","family":"Kapp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Mas\u2010Moruno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Joner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,6]]},"reference":[{"key":"e_1_2_6_1_2","unstructured":"\u00a0"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra051091"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-12-200606200-00009"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.09.042"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.71.220"},{"key":"e_1_2_6_6_2","unstructured":"\u00a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00019501-200409000-00003"},{"key":"e_1_2_6_8_2","first-page":"567","volume":"57","author":"Byrne R. 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