Immune stealth VP28-conjugated heparin nanocomplex development for reducing self-aggregation risk of heparin*

Unfractionated heparins (heparin) 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, self-aggregation induced life-threatening complications. We proposed that the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. Therefore, an immunostealth recombinant viral capsid protein (VP28) was conjugated with heparin to form a novel nanocomplex (VP28-heparin). The size of VP28-heparin nanocomplexes is approximately 9 nm and this small particle does not induce immune responses in animal model systems. Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dose in vivo. Thus, an effective and safe heparin derivative, VP28-heparin, has been developed as proposed and may be used for biomedical applications.