Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation

• Main Authors: Hussein, Hussein Reda, Chang, Chia-Yu, Zheng, Yini, Yang, Chih-Yu, Li, Li-Hua, Lee, Yi-Tzu, Chen, Jun-Yi, Liang, Yu-Chaun, Lin, Chuan-Ju, Chang, Yu-Chia, Geo, Hui Nee, Noor, Suzita Mohd, Kiew, Lik Voon, Chen, Fu-Rong, Chang, Chia-Ching
• Format: Article
• Published: Institute of Physics 2024
• Subjects: QC Physics
• Online Access: http://eprints.um.edu.my/44752/; https://doi.org/10.1088/1361-6528/ad21a2

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.