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

Hussein Reda Hussein, Chia Yu Chang, Yini Zheng, Chih Yu Yang, Li Hua Li, Yi Tzu Lee, Jun Yi Chen, Yu Chaun Liang, Chuan Ju Lin, Yu Chia Chang, Hui Nee Geo, Suzita Mohd Noor, Lik Voon Kiew, Fu Rong Chen, Chia Ching Chang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Article number175102
JournalNanotechnology
Volume35
Issue number17
DOIs
StatePublished - 22 Apr 2024

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

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