دورية أكاديمية
Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation.
العنوان: | Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation. |
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المؤلفون: | Hussein HR; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan.; Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut branch 71524, Egypt., Chang CY; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan., Zheng Y; Department of Materials Science and Engineering, City University of Hong Kong, Hong Kong., Yang CY; Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan., Li LH; Department of Pathology and laboratory medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan., Lee YT; Department of Emergency, Taipei Veterans General Hospital, Taipei 11217, Taiwan., Chen JY; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan., Liang YC; Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan., Lin CJ; Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan., Chang YC; Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan., Geo HN; Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia., Noor SM; Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia., Kiew LV; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan.; Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia., Chen FR; Department of Materials Science and Engineering, City University of Hong Kong, Hong Kong., Chang CC; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan.; Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan.; Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan.; International College of Semiconductor Technology, National Yang Ming Chiao Tung University, 30010 Hsinchu, Taiwan.; Institute of Physics, Academia Sinica, Taipei 10529, Taiwan. |
المصدر: | Nanotechnology [Nanotechnology] 2024 Feb 09; Vol. 35 (17). Date of Electronic Publication: 2024 Feb 09. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: IOP Pub Country of Publication: England NLM ID: 101241272 Publication Model: Electronic Cited Medium: Internet ISSN: 1361-6528 (Electronic) Linking ISSN: 09574484 NLM ISO Abbreviation: Nanotechnology Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Bristol, UK : IOP Pub., c1990- |
مواضيع طبية MeSH: | Heparin*/pharmacology , Heparin*/therapeutic use , Thrombocytopenia*/drug therapy, Animals ; Mice ; Anticoagulants/pharmacology ; Blood Coagulation ; Platelet Count |
مستخلص: | Heparins are a family of sulfated linear negatively charged polysaccharides that have been widely used for their anticoagulant, antithrombotic, antitumor, anti-inflammatory, and antiviral properties. Additionally, it has been used for acute cerebral infarction relief as well as other pharmacological actions. However, heparin's self-aggregated macrocomplex may reduce blood circulation time and induce life-threatening thrombocytopenia (HIT) complicating the use of heparins. Nonetheless, the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. An immunostealth recombinant viral capsid protein (VP28) was expressed and conjugated with heparin to form a novel nanoparticle (VP28-heparin). VP28-heparin was characterized and tested to determine its immunogenicity, anticoagulation properties, effects on total platelet count, and risk of inducing HIT in animal models. The synthesized VP28-heparin trimeric nanoparticle was non-immunogenic, possessed an average hydrodynamic size (8.81 ± 0.58 nm) optimal for the evasion renal filtration and reticuloendothelial system uptake (hence prolonging circulating half-life). Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dose in vivo (hence reducing HIT risks). The VP28-heparin nanoparticle also exhibited superior anticoagulation properties (2.2× higher prothrombin time) and comparable activated partial thromboplastin time, but longer anticoagulation period when compared to unfractionated heparin. The anticoagulative effects of the VP28-heparin can also be reversed using protamine sulfate. Thus, VP28-heparin may be an effective and safe heparin derivative for therapeutic use. (© 2024 IOP Publishing Ltd.) |
فهرسة مساهمة: | Keywords: VP28 protein of white spot syndrome virus (WSSV); VP28-Heparin nanoparticle; activated partial thromboplastin time (aPTT); heparin; heparin-induced thrombocytopenia (HIT); self-assembly of heparin |
المشرفين على المادة: | 9005-49-6 (Heparin) 0 (Anticoagulants) |
تواريخ الأحداث: | Date Created: 20240123 Date Completed: 20240214 Latest Revision: 20240216 |
رمز التحديث: | 20240216 |
DOI: | 10.1088/1361-6528/ad21a2 |
PMID: | 38262054 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1361-6528 |
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DOI: | 10.1088/1361-6528/ad21a2 |