Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

Hung-Wei Yang,1,* Mu-Yi Hua,1,* Kun-Ju Lin,2,* Shiaw-Pyng Wey,3 Rung-Ywan Tsai,4 Siao-Yun Wu,5 Yi-Ching Lu,5 Hao-Li Liu,6 Tony Wu,7 Yunn-Hwa Ma5 1Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, 2Molecular Imaging Center, Department of Nuclear Medicine...

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Autores principales:	Yang HW, Hua MY, Lin KJ, Wey SP, Tsai RY, Wu SY, Lu YC, Liu HL, Wu T, Ma YH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bc306f457d624f3fb0c2b15c2dc67095
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spelling	oai:doaj.org-article:bc306f457d624f3fb0c2b15c2dc670952021-12-02T01:07:53ZBioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis1176-91141178-2013https://doaj.org/article/bc306f457d624f3fb0c2b15c2dc670952012-10-01T00:00:00Zhttp://www.dovepress.com/bioconjugation-of-recombinant-tissue-plasminogen-activator-to-magnetic-a11159https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Hung-Wei Yang,1,* Mu-Yi Hua,1,* Kun-Ju Lin,2,* Shiaw-Pyng Wey,3 Rung-Ywan Tsai,4 Siao-Yun Wu,5 Yi-Ching Lu,5 Hao-Li Liu,6 Tony Wu,7 Yunn-Hwa Ma5 1Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, 2Molecular Imaging Center, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China; 3Department of Medical Imaging and Radiological Sciences, 4Electronics and Optoelectronics Research Laboratories, Industrial Technology Research Institute, Hsin-chu, Taiwan, Republic of China; 5Department of Physiology and Pharmacology and Healthy Aging Research Center, 6Department of Electrical Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China; 7Department of Neurology, Chang Gung University College of Medicine and Memorial Hospital, Tao-Yuan, Taiwan, Republic of China*These authors contributed equally to this workAbstract: Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 &micro;g of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4&deg;C and 25&deg;C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 &plusmn; 3.2 minutes to 10.8 &plusmn; 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15&ndash;25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases.Keywords: thrombolysis, recombinant tissue plasminogen activator, magnetic nanocarriers, magnetic targeting, targeting therapyYang HWHua MYLin KJWey SPTsai RYWu SYLu YCLiu HLWu TMa YHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5159-5173 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Yang HW Hua MY Lin KJ Wey SP Tsai RY Wu SY Lu YC Liu HL Wu T Ma YH Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis
description	Hung-Wei Yang,1,* Mu-Yi Hua,1,* Kun-Ju Lin,2,* Shiaw-Pyng Wey,3 Rung-Ywan Tsai,4 Siao-Yun Wu,5 Yi-Ching Lu,5 Hao-Li Liu,6 Tony Wu,7 Yunn-Hwa Ma5 1Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, 2Molecular Imaging Center, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China; 3Department of Medical Imaging and Radiological Sciences, 4Electronics and Optoelectronics Research Laboratories, Industrial Technology Research Institute, Hsin-chu, Taiwan, Republic of China; 5Department of Physiology and Pharmacology and Healthy Aging Research Center, 6Department of Electrical Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China; 7Department of Neurology, Chang Gung University College of Medicine and Memorial Hospital, Tao-Yuan, Taiwan, Republic of China*These authors contributed equally to this workAbstract: Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 &micro;g of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4&deg;C and 25&deg;C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 &plusmn; 3.2 minutes to 10.8 &plusmn; 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15&ndash;25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases.Keywords: thrombolysis, recombinant tissue plasminogen activator, magnetic nanocarriers, magnetic targeting, targeting therapy
format	article
author	Yang HW Hua MY Lin KJ Wey SP Tsai RY Wu SY Lu YC Liu HL Wu T Ma YH
author_facet	Yang HW Hua MY Lin KJ Wey SP Tsai RY Wu SY Lu YC Liu HL Wu T Ma YH
author_sort	Yang HW
title	Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis
title_short	Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis
title_full	Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis
title_fullStr	Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis
title_full_unstemmed	Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis
title_sort	bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/bc306f457d624f3fb0c2b15c2dc67095
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Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

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