Hussein, Hussein Reda and Chang, Chia-Yu and Zheng, Yini and Yang, Chih-Yu and Li, Li-Hua and Lee, Yi-Tzu and Chen, Jun-Yi and Liang, Yu-Chaun and Lin, Chuan-Ju and Chang, Yu-Chia and Geo, Hui Nee and Noor, Suzita Mohd and Kiew, Lik Voon and Chen, Fu-Rong and Chang, Chia-Ching (2024) Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation. Nanotechnology, 35 (17). ISSN 1361-6528, DOI https://doi.org/10.1088/1361-6528/ad21a2.
Full text not available from this repository.Abstract
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.
| Item Type: | Article |
|---|---|
| Funders: | National Science and Technology Council, Taiwanhttps://doi.org/10.13039/501100020950 [NSTC 112-2112-M-A49-003], National Science and Technology Council, Taiwanhttps://doi.org/10.13039/501100020950 [112-2927-I-A49-001], National Science and Technology Council, Taiwanhttps://doi.org/10.13039/501100020950 [111-2112-M-A49-025], National Science and Technology Council, Taiwanhttps://doi.org/10.13039/501100020950 [111-2321-B-A49-007], National Science and Technology Council, Taiwanhttps://doi.org/10.13039/501100020950 [111-2927-I-A49-004], National Science and Technology Council, Taiwanhttps://doi.org/10.13039/501100020950 [110-2923-M-009-005-MY3], National Science and Technology Council of Taiwan, Center for Intelligent Drug Systems and Smart Biodevices (IDS2B) of NYCU, Higher Education Sprout Project of the Ministry of Education (MOE), Taiwan |
| Uncontrolled Keywords: | Platelets; Polysaccharides; Recombinant proteins; Self assembly; Sulfur compounds; Synthesis (chemical); Viruses; anticoagulant agent; capsid protein; heparin; heparin derivative; nanoparticle; polysaccharide; protamine sulfate; Activated partial thromboplastin time; Anti-coagulation; Heparin; Heparin-induced thrombocytopenium; Self-assembly of heparin; Thrombocytopenia; Vp28 protein of white spot syndrome virus; Vp28-heparin nanoparticle; White spot syndrome virus; activated partial thromboplastin time; animal model; anticoagulation; antineoplastic activity; antiviral activity; article; brain infarction; cancer inhibition; circulation time; conjugation; controlled study; drug mechanism; drug therapy; female; genetic recombination; glomerulus filtration; half life time; heparin induced thrombocytopenia; human; hydrodynamics; immunogenicity; male; mouse; nonhuman; platelet count; prothrombin time; reticuloendothelial system; surgical planning system; thrombocytopenia; virus capsid; White spot syndrome virus; Nanoparticles |
| Subjects: | Q Science > QC Physics |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 11 Jul 2024 05:36 |
| Last Modified: | 11 Jul 2024 05:36 |
| URI: | http://eprints.um.edu.my/id/eprint/44752 |
Actions (login required)
 |
View Item |
