Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle

Jyh-Ping Chen,1 Pei-Ching Yang,1 Yunn-Hwa Ma,2 Su-Ju Tu,3 Yu-Jen Lu1,41Department of Chemical and Materials Engineering, 2Department of Physiology and Pharmacology, 3Department of Medical Imaging and Radiological Sciences, Chang Gung University, Kwei-San, Taoyuan, Taiwan, Republic of China; 4Departm...

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Autores principales:	Chen JP, Yang PC, Ma YH, Tu SJ, Lu YJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d64ce733fbfa48769565e1640e79be68
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spelling	oai:doaj.org-article:d64ce733fbfa48769565e1640e79be682021-12-02T02:04:18ZTargeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle1176-91141178-2013https://doaj.org/article/d64ce733fbfa48769565e1640e79be682012-09-01T00:00:00Zhttp://www.dovepress.com/targeted-delivery-of-tissue-plasminogen-activator-by-binding-to-silica-a11124https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Jyh-Ping Chen,1 Pei-Ching Yang,1 Yunn-Hwa Ma,2 Su-Ju Tu,3 Yu-Jen Lu1,41Department of Chemical and Materials Engineering, 2Department of Physiology and Pharmacology, 3Department of Medical Imaging and Radiological Sciences, Chang Gung University, Kwei-San, Taoyuan, Taiwan, Republic of China; 4Department of Neurosurgery, Chang Gung Memorial Hospital, Kwei-San, Taoyuan, Taiwan, Republic of ChinaBackground and methods: Silica-coated magnetic nanoparticle (SiO2-MNP) prepared by the sol-gel method was studied as a nanocarrier for targeted delivery of tissue plasminogen activator (tPA). The nanocarrier consists of a superparamagnetic iron oxide core and an SiO2 shell and is characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, superconducting quantum interference device, and thermogravimetric analysis. An amine-terminated surface silanizing agent (3-aminopropyltrimethoxysilane) was used to functionalize the SiO2 surface, which provides abundant &mdash;NH2 functional groups for conjugating with tPA.Results: The optimum drug loading is reached when 0.5 mg/mL tPA is conjugated with 5 mg SiO2-MNP where 94% tPA is attached to the carrier with 86% retention of amidolytic activity and full retention of fibrinolytic activity. In vitro biocompatibility determined by lactate dehydrogenase release and cell proliferation indicated that SiO2-MNP does not elicit cytotoxicity. Hematological analysis of blood samples withdrawn from mice after venous administration indicates that tPA-conjugated SiO2-MNP (SiO2-MNP-tPA) did not alter blood component concentrations. After conjugating to SiO2-MNP, tPA showed enhanced storage stability in buffer and operation stability in whole blood up to 9.5 and 2.8-fold, respectively. Effective thrombolysis with SiO2-MNP-tPA under magnetic guidance is demonstrated in an ex vivo thrombolysis model where 34% and 40% reductions in blood clot lysis time were observed compared with runs without magnetic targeting and with free tPA, respectively, using the same drug dosage. Enhanced penetration of SiO2-MNP-tPA into blood clots under magnetic guidance was confirmed from microcomputed tomography analysis.Conclusion: Biocompatible SiO2-MNP developed in this study will be useful as a magnetic targeting drug carrier to improve clinical thrombolytic therapy.Keywords: magnetic nanoparticles, drug delivery, thrombolysis, tissue plasminogen activator, silicaChen JPYang PCMa YHTu SJLu YJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 5137-5149 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen JP Yang PC Ma YH Tu SJ Lu YJ Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle
description	Jyh-Ping Chen,1 Pei-Ching Yang,1 Yunn-Hwa Ma,2 Su-Ju Tu,3 Yu-Jen Lu1,41Department of Chemical and Materials Engineering, 2Department of Physiology and Pharmacology, 3Department of Medical Imaging and Radiological Sciences, Chang Gung University, Kwei-San, Taoyuan, Taiwan, Republic of China; 4Department of Neurosurgery, Chang Gung Memorial Hospital, Kwei-San, Taoyuan, Taiwan, Republic of ChinaBackground and methods: Silica-coated magnetic nanoparticle (SiO2-MNP) prepared by the sol-gel method was studied as a nanocarrier for targeted delivery of tissue plasminogen activator (tPA). The nanocarrier consists of a superparamagnetic iron oxide core and an SiO2 shell and is characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, superconducting quantum interference device, and thermogravimetric analysis. An amine-terminated surface silanizing agent (3-aminopropyltrimethoxysilane) was used to functionalize the SiO2 surface, which provides abundant &mdash;NH2 functional groups for conjugating with tPA.Results: The optimum drug loading is reached when 0.5 mg/mL tPA is conjugated with 5 mg SiO2-MNP where 94% tPA is attached to the carrier with 86% retention of amidolytic activity and full retention of fibrinolytic activity. In vitro biocompatibility determined by lactate dehydrogenase release and cell proliferation indicated that SiO2-MNP does not elicit cytotoxicity. Hematological analysis of blood samples withdrawn from mice after venous administration indicates that tPA-conjugated SiO2-MNP (SiO2-MNP-tPA) did not alter blood component concentrations. After conjugating to SiO2-MNP, tPA showed enhanced storage stability in buffer and operation stability in whole blood up to 9.5 and 2.8-fold, respectively. Effective thrombolysis with SiO2-MNP-tPA under magnetic guidance is demonstrated in an ex vivo thrombolysis model where 34% and 40% reductions in blood clot lysis time were observed compared with runs without magnetic targeting and with free tPA, respectively, using the same drug dosage. Enhanced penetration of SiO2-MNP-tPA into blood clots under magnetic guidance was confirmed from microcomputed tomography analysis.Conclusion: Biocompatible SiO2-MNP developed in this study will be useful as a magnetic targeting drug carrier to improve clinical thrombolytic therapy.Keywords: magnetic nanoparticles, drug delivery, thrombolysis, tissue plasminogen activator, silica
format	article
author	Chen JP Yang PC Ma YH Tu SJ Lu YJ
author_facet	Chen JP Yang PC Ma YH Tu SJ Lu YJ
author_sort	Chen JP
title	Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle
title_short	Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle
title_full	Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle
title_fullStr	Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle
title_full_unstemmed	Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle
title_sort	targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/d64ce733fbfa48769565e1640e79be68
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Targeted delivery of tissue plasminogen activator by binding to silica-coated magnetic nanoparticle

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