title: Local gene delivery via endovascular stents coated with dodecylated chitosan-plasmid DNA nanoparticles.
abstract: Development of efficacious therapeutic strategies to prevent and inhibit the occurrences of restenosis after percutaneous transluminal coronary angioplasty is critical for the treatment of cardiovascular diseases. In this study, the feasibility and efficiency of stents coated with dodecylated chitosan-plasmid DNA nanoparticles (DCDNPs) were evaluated as scaffolds for localized and prolonged delivery of reporter genes into the diseased blood vessel wall. Dodecylated chitosan-plasmid DNA complexes formed stable positive charged nanospheres with mean diameter of approximately 90-180 nm and zeta potential of +28 ± 3 mV. As prepared DCDNPs were spray-coated on stents, a thin layer of dense DCDNPs was successfully distributed onto the metal struts of the endovascular stents as demonstrated by scanning electron microscopy. The DCDNP stents were characterized for the release kinetics of plasmid DNA, and further evaluated for gene delivery and expression both in vitro and in vivo. In cell culture, DCDNP stents containing plasmid EGFP-C1 exhibited high level of GFP expression in cells grown on the stent surface and along the adjacent area. In animal studies, reporter gene activity was observed in the region of the artery in contact with the DCDNP stents, but not in adjacent arterial segments or distal organs. The DCDNP stent provides a very promising strategy for cardiovascular gene therapy.
authors.affiliation: Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Dunwan
authors.initials: D
authors.lastname: Zhu
authors.forename: Xu
authors.initials: X
authors.lastname: Jin
authors.forename: Xigang
authors.initials: X
authors.lastname: Leng
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.forename: Junbo
authors.initials: J
authors.lastname: Bao
authors.forename: Wenguang
authors.initials: W
authors.lastname: Liu
authors.forename: Kangde
authors.initials: K
authors.lastname: Yao
authors.forename: Cunxian
authors.initials: C
authors.lastname: Song
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D017536:Carotid Artery, Common; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004270:DNA, Circular / Q000008:administration & dosage* / Q000737:chemistry; D054855:Drug-Eluting Stents; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D008164:Luminescent Proteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D014162:Transfection
chemical_list: D004270:DNA, Circular; D008164:Luminescent Proteins; D048271:Chitosan