title: Enzyme-functionalized vascular grafts catalyze in-situ release of nitric oxide from exogenous NO prodrug.
abstract: Nitric oxide (NO) is an important signaling molecule in cardiovascular system, and the sustained release of NO by endothelial cells plays a vital role in maintaining patency and homeostasis. In contrast, lack of endogenous NO in artificial blood vessel is believed to be the main cause of thrombus formation. In this study, enzyme prodrug therapy (EPT) technique was employed to construct a functional vascular graft by immobilization of galactosidase on the graft surface. The enzyme-functionalized grafts exhibited excellent catalytic property in decomposition of the exogenously administrated NO prodrug. Localized and on-demand release of NO was demonstrated by in vitro release assay and fluorescent probe tracing in an ex vivo model. The immobilized enzyme retained catalytic property even after subcutaneous implantation of the grafts for one month. The functional vascular grafts were implanted into the rat abdominal aorta with a 1-month monitoring period. Results showed effective inhibition of thrombus formation in vivo and enhancement of vascular tissue regeneration and remodeling on the grafts. Thus, we create an enzyme-functionalized vascular graft that can catalyze prodrug to release NO locally and sustainably, indicating that this approach may be useful to develop new cell-free vascular grafts for treatment of vascular diseases.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300071, PR China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Kang
authors.initials: K
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300071, PR China.
authors.forename: Yingping
authors.initials: Y
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China; Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300071, PR China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300071, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Cardiovascular Division, King's College London BHF Centre, London, United Kingdom.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China; Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering Tianjin, College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: qiangzhao@nankai.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal; D001807:Blood Vessel Prosthesis; D002384:Catalysis; D004800:Enzymes, Immobilized / Q000008:administration & dosage* / Q000627:therapeutic use; D005696:Galactosidases / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011091:Polyesters / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004800:Enzymes, Immobilized; D011091:Polyesters; D011355:Prodrugs; C016240:polycaprolactone; D009569:Nitric Oxide; D005696:Galactosidases
keywords: Controlled release; Enzyme prodrug therapy (EPT); Nitric oxide; Tissue regeneration; Vascular grafts