期刊
BIOMATERIALS
卷 34, 期 6, 页码 1635-1643出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.11.006
关键词
Coronary stents; VEGF; Paclitaxel; Restenosis; Gene and drug delivery
资金
- NSFC
- MOST [50830106, 50873114, 81271706, 30800225, 50903093, 81171478, 2012EG150136]
Long-term clinical studies of drug-eluting stents (DES) have reported high incidence of late thrombosis. Given the growing concern over the clinical application of this technology, we have developed a stent coated with hi-layered PLGA nanoparticles (BL-PLGA NPs) containing VEGF plasmid in the outer layer and paclitaxel (PTX) in the inner core (VEGF/PTX NPs). We hypothesized that early release of VEGF gene would promote re-endothelialization, while slow release of PTX would suppress smooth muscle cell proliferation. Using Fc plasmid as a reporter gene, we observed that Fc/PTX NPs successfully expressed Fc protein, but did not show cytotoxicity or anti-proliferative effect during the first 7 days in cell culture. In contrast, PTX NPs showed strong anti-proliferative effect staring from day I in culture, suggesting sequential release of gene and PTX from the BL-PLGA NPs. In vivo effects of the treated stent were assessed in mini-swines. Implantation of GFP/PTX NP-coated stents revealed efficient local GFP gene transfection at day 7. VEGF/PTX NP-coated stents showed complete re-endothelialization and significantly suppressed in-stent restenosis after 1 month compared to commercial DES. In conclusion, the VEGF/PTX NP-coated stents promote early endothelium healing while inhibit smooth muscle cell proliferation through sequential release of the VEGF gene and paclitaxel. (C) 2012 Elsevier Ltd. All rights reserved.
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