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

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

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...

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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:	R Medicine
Online Access:	http://eprints.um.edu.my/45296/ https://doi.org/10.1088/1361-6528/ad21a2
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spelling	my.um.eprints.452962024-10-07T08:24:04Z http://eprints.um.edu.my/45296/ Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation 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 R Medicine 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. Institute of Physics 2024-04 Article PeerReviewed 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 <https://doi.org/10.1088/1361-6528/ad21a2>. https://doi.org/10.1088/1361-6528/ad21a2 10.1088/1361-6528/ad21a2
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine 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 Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation
description	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.
format	Article
author	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
author_facet	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
author_sort	Hussein, Hussein Reda
title	Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation
title_short	Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation
title_full	Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation
title_fullStr	Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation
title_full_unstemmed	Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation
title_sort	immune-stealth vp28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation
publisher	Institute of Physics
publishDate	2024
url	http://eprints.um.edu.my/45296/ https://doi.org/10.1088/1361-6528/ad21a2
_version_	1814047536142352384
score	13.211869

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

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