PMID- 38262054 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240216 IS - 1361-6528 (Electronic) IS - 0957-4484 (Linking) VI - 35 IP - 17 DP - 2024 Feb 9 TI - Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation. LID - 10.1088/1361-6528/ad21a2 [doi] AB - 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 dosein 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. CI - (c) 2024 IOP Publishing Ltd. FAU - Hussein, Hussein Reda AU - Hussein HR AD - Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan. AD - Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Assiut branch 71524, Egypt. FAU - Chang, Chia-Yu AU - Chang CY AUID- ORCID: 0000-0002-4077-5607 AD - Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan. FAU - Zheng, Yini AU - Zheng Y AD - Department of Materials Science and Engineering, City University of Hong Kong, Hong Kong. FAU - Yang, Chih-Yu AU - Yang CY AUID- ORCID: 0000-0001-9899-3159 AD - Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. AD - Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. FAU - Li, Li-Hua AU - Li LH AD - Department of Pathology and laboratory medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan. FAU - Lee, Yi-Tzu AU - Lee YT AD - Department of Emergency, Taipei Veterans General Hospital, Taipei 11217, Taiwan. FAU - Chen, Jun-Yi AU - Chen JY AD - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan. FAU - Liang, Yu-Chaun AU - Liang YC AD - Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan. FAU - Lin, Chuan-Ju AU - Lin CJ AD - Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan. FAU - Chang, Yu-Chia AU - Chang YC AD - Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan. FAU - Geo, Hui Nee AU - Geo HN AD - Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. FAU - Noor, Suzita Mohd AU - Noor SM AD - Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. FAU - Kiew, Lik Voon AU - Kiew LV AD - Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan. AD - Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia. FAU - Chen, Fu-Rong AU - Chen FR AD - Department of Materials Science and Engineering, City University of Hong Kong, Hong Kong. FAU - Chang, Chia-Ching AU - Chang CC AUID- ORCID: 0000-0002-3444-0894 AD - Department of Biological Science and Technology, National Yang Ming Chiao Tung University, 30068 Hsinchu, Taiwan. AD - Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan. AD - Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan. AD - International College of Semiconductor Technology, National Yang Ming Chiao Tung University, 30010 Hsinchu, Taiwan. AD - Institute of Physics, Academia Sinica, Taipei 10529, Taiwan. LA - eng PT - Journal Article DEP - 20240209 PL - England TA - Nanotechnology JT - Nanotechnology JID - 101241272 RN - 9005-49-6 (Heparin) RN - 0 (Anticoagulants) SB - IM MH - Animals MH - Mice MH - *Heparin/pharmacology/therapeutic use MH - Anticoagulants/pharmacology MH - Blood Coagulation MH - *Thrombocytopenia/drug therapy MH - Platelet Count OTO - NOTNLM OT - VP28 protein of white spot syndrome virus (WSSV) OT - VP28-Heparin nanoparticle OT - activated partial thromboplastin time (aPTT) OT - heparin OT - heparin-induced thrombocytopenia (HIT) OT - self-assembly of heparin EDAT- 2024/01/23 18:42 MHDA- 2024/02/10 22:54 CRDT- 2024/01/23 17:41 PHST- 2023/11/16 00:00 [received] PHST- 2024/01/23 00:00 [accepted] PHST- 2024/02/10 22:54 [medline] PHST- 2024/01/23 18:42 [pubmed] PHST- 2024/01/23 17:41 [entrez] AID - 10.1088/1361-6528/ad21a2 [doi] PST - epublish SO - Nanotechnology. 2024 Feb 9;35(17). doi: 10.1088/1361-6528/ad21a2.