{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:30:10Z","timestamp":1792031410465,"version":"4.4.0"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T00:00:00Z","timestamp":1582502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005866","name":"Far Eastern Memorial Hospital","doi-asserted-by":"publisher","award":["106DN21"],"award-info":[{"award-number":["106DN21"]}],"id":[{"id":"10.13039\/501100005866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In-stent restenosis is a serious concern for patients treated through the stenting procedure, although this can be solved using drug-eluting stents and\/or drug-eluting balloon catheters. However, the chemical agents released from the drug-eluting layer for inhibiting smooth muscle cell (SMC) migration are inevitably associated with damage to vascular endothelial cell (ECs). The present in vitro study used a distinct strategy, in which a smart gene (phEGR1-PKC\u03b4, an engineered plasmid consists of an SMC-specific promoter (human early growth response 1, hEGR1 promoter) ligated with a gene encoding apoptosis-inducing protein (protein kinase C-delta, PKC\u03b4) was incorporated into a novel gene vehicle (Au cluster-incorporated polyethylenimine\/carboxymethyl hexanoyl chitosan, PEI-Au\/CHC) to form the PEI-Au\/CHC\/phEGR1-PKC\u03b4 complex, which was proposed for the selective inhibition of SMC proliferation. It was found that the cell viability of SMCs receiving the PEI-Au\/CHC\/phEGR1-PKC\u03b4 complex under simulated inflammation conditions was significantly lower than that of the ECs receiving the same treatment. In addition, the PEI-Au\/CHC\/phEGR1-PKC\u03b4 complex did not demonstrate an inhibitory effect on EC proliferation and migration under simulated inflammation conditions. Finally, the PEI-Au\/CHC\/phEGR1-PKC\u03b4 complexes coated onto a balloon catheter used in percutaneous transluminal coronary angioplasty (PTCA) could be transferred to both the ECs and the SMC layer of Sprague Dawley (SD) rat aortas ex vivo. These preliminary in vitro results suggest that the newly developed approach proposed in the present study might be a potential treatment for reducing the incidence rate of in-stent restenosis and late thrombosis in the future.<\/jats:p>","DOI":"10.3390\/ijms21041530","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T04:21:26Z","timestamp":1582604486000},"page":"1530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An Engineered Gene Nanovehicle Developed for Smart Gene Therapy to Selectively Inhibit Smooth Muscle Cells: An In Vitro Study"],"prefix":"10.3390","volume":"21","author":[{"given":"Ling-Yi","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Taipei Municipal Wanfang Hospital, Taipei 11696, Taiwan"},{"name":"Graduate Institute of Nanomedicine and Medical Engineering, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-I","family":"Tung","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Taipei City Hospital, Taipei 11146, Taiwan"},{"name":"Department of Health and Welfare, College of City Management, University of Taipei, Taipei 10048, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Ming","family":"Chiu","sequence":"additional","affiliation":[{"name":"Far Eastern Memorial Hospital, Taipei 22060, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-420X","authenticated-orcid":false,"given":"Tse-Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Frosteg\u00e5rd, J. (2013). Immunity, atherosclerosis and cardiovascular disease. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-117"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1161\/01.CIR.0000019122.00032.DF","article-title":"Restenosis: Repeat narrowing of a coronary artery prevention and treatment","volume":"105","author":"Dangas","year":"2002","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jvs.2006.09.053","article-title":"Protein kinase C-\u03b4 regulates migration and proliferation of vascular smooth muscle cells through the extracellular signal-regulated kinase 1\/2","volume":"45","author":"Liu","year":"2007","journal-title":"J. Vasc. Surg."},{"key":"ref_4","first-page":"865","article-title":"Proteomic analysis identifies nuclear protein effectors in PKC-\u03b4 signaling under high glucose-induced apoptosis in human umbilical vein endothelial cells","volume":"4","author":"Sun","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.4049\/jimmunol.147.11.3981","article-title":"Expression of protein kinase C genes in hemopoietic cells is cell-type-and B cell-differentiation stage specific","volume":"147","author":"Mischak","year":"1991","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1006\/bbrc.2000.4123","article-title":"The overexpression of PKC\u03b4 is involved in vascular endothelial growth factor-resistant apoptosis in cultured primary sinusoidal endothelial cells","volume":"280","author":"Takahashi","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"H2253","DOI":"10.1152\/ajpheart.00274.2009","article-title":"Caspase-mediated protein kinase C-\u03b4 cleavage is necessary for apoptosis of vascular smooth muscle cells","volume":"297","author":"Kato","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1161\/01.CIR.100.9.967","article-title":"Requirement for protein kinase C in reactive oxygen species\u2013induced apoptosis of vascular smooth muscle cells","volume":"100","author":"Li","year":"1999","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10149","DOI":"10.1073\/pnas.89.21.10149","article-title":"Ionizing radiation activates transcription of the EGR1 gene via CArG elements","volume":"89","author":"Datta","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"L817","DOI":"10.1152\/ajplung.00190.2003","article-title":"Induction of early growth-response factor 1 by platelet-derived growth factor in human airway smooth muscle","volume":"286","author":"Hjoberg","year":"2004","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1038\/71020","article-title":"New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury","volume":"5","author":"Santiago","year":"1999","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9138","DOI":"10.1073\/pnas.1233634100","article-title":"Conjugation to gold nanoparticles enhances polyethylenimine\u2019s transfer of plasmid DNA into mammalian cells","volume":"100","author":"Thomas","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0005-2736(98)00199-0","article-title":"Interactions of polymeric and liposomal gene delivery systems with extracellular glycosaminoglycans: Physicochemical and transfection studies","volume":"1415","author":"Ruponen","year":"1999","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/337387a0","article-title":"Cationic liposome-mediated transfection","volume":"337","author":"Felgner","year":"1989","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6982","DOI":"10.1073\/pnas.86.18.6982","article-title":"Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA","volume":"86","author":"Behr","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18997","DOI":"10.1074\/jbc.270.32.18997","article-title":"Cellular and molecular barriers to gene transfer by a cationic lipid","volume":"270","author":"Zabner","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7297","DOI":"10.1073\/pnas.92.16.7297","article-title":"A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine","volume":"92","author":"Boussif","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/sj.gt.3300454","article-title":"The influence of polymer structure on the interactions of cationic polymers with DNA and morphology of the resulting complexes","volume":"4","author":"Tang","year":"1997","journal-title":"Gene Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5616","DOI":"10.1021\/bi9602019","article-title":"Mechanism of DNA release from cationic liposome\/DNA complexes used in cell transfection","volume":"35","author":"Xu","year":"1996","journal-title":"Biochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s11095-006-9224-x","article-title":"Novel liposomal formulation for targeted gene delivery","volume":"24","author":"Rivest","year":"2007","journal-title":"Pharm. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"40493","DOI":"10.1038\/srep40493","article-title":"Intracellular accumulation of gold nanoparticles leads to inhibition of macropinocytosis to reduce the endoplasmic reticulum stress","volume":"7","author":"Gunduz","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1038\/s41598-019-40579-6","article-title":"Cationic gold nanoparticles elicit mitochondrial dysfunction: A multi-omics study","volume":"9","author":"Gallud","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.imlet.2008.07.002","article-title":"LPS induces inflammatory responses in human aortic vascular smooth muscle cells via Toll-like receptor 4 expression and nitric oxide production","volume":"120","author":"Heo","year":"2008","journal-title":"Immunol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/gt.2017.13","article-title":"Live-cell imaging to compare the transfection and gene silencing efficiency of calcium phosphate nanoparticles and a liposomal transfection agent","volume":"24","author":"Chernousova","year":"2017","journal-title":"Gene Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1177\/153303460900800605","article-title":"Optimization of a new non-viral vector for transfection: Eudragit nanoparticles for the delivery of a DNA plasmid","volume":"8","author":"Gargouri","year":"2009","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.jfma.2018.08.026","article-title":"Developing a novel cholesterol-based nanocarrier with high transfection efficiency and serum compatibility for gene therapy","volume":"118","author":"Chang","year":"2019","journal-title":"J. Formos. Med. 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