title: Development of antithrombotic nanoconjugate blocking integrin α2β1-collagen interactions.
abstract: An antithrombotic nanoconjugate was designed in which a designed biomimetic peptide LWWNSYY was immobilized to the surface of poly(glycidyl methacrylate) nanoparticles (PGMA NPs). Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin α2β1-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a Kd of 3.45 ± 1.06 μM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion in vitro with a reduced IC50 of 1.83 ± 0.29 μg/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed in vivo with a 50% reduction of thrombus weight. Therefore, L-PGMA NPs were developed as a high-efficiency antithrombotic nanomedicine targeted for collagen exposed on diseased blood vessel wall.
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: Departments of Chemical Engineering and Bioengineering, University of Washington, Seattle, WA 98192, USA.
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Departments of Chemical Engineering and Bioengineering, University of Washington, Seattle, WA 98192, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Fujihara
authors.affiliation: Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D040761:Biomimetic Materials; D003094:Collagen / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology*; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008297:Male; D058726:Nanoconjugates / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D011109:Polymethacrylic Acids / Q000737:chemistry; D011485:Protein Binding; D017208:Rats, Wistar; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy
chemical_list: D005343:Fibrinolytic Agents; D038982:Integrin alpha2beta1; D058726:Nanoconjugates; D009842:Oligopeptides; D011109:Polymethacrylic Acids; C042535:polyglycidyl methacrylate; D003094:Collagen