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). p. 175102. ISSN 0957-4484, 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 (2.2x 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.
| Item Type: | Article |
|---|---|
| Funders: | National Science and Technology Council, Taiwan https://doi.org/10.13039/501100020950 (NSTC 112-2112-M-A49-003) ; (112-2927-I-A49-001) ; (111-2112-M-A49-025) ; (111-2321-B-A49-007) ; (111-2927-I-A49-004) ; (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: | VP28 protein of white spot syndrome virus (WSSV); heparin; VP28-Heparin nanoparticle; activated partial thromboplastin time (aPTT); self-assembly of heparin; heparin-induced thrombocytopenia (HIT) |
| Subjects: | R Medicine |
| Divisions: | Faculty of Medicine Faculty of Medicine > Biomedical Science Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 07 Oct 2024 08:24 |
| Last Modified: | 07 Oct 2024 08:24 |
| URI: | http://eprints.um.edu.my/id/eprint/45296 |
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