Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles

Jie Zhou,1,* Jian Zhang,2,* Wenxi Gao11Department of Urology, Hubei Hospital of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA*Th...

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Main Authors: Zhou J, Zhang J, Gao W
Format: Article
Language:English
Published: Dove Medical Press 2014-06-01
Series:International Journal of Nanomedicine
Online Access:http://www.dovepress.com/enhanced-and-selective-delivery-of-enzyme-therapy-to-9l-glioma-tumor-v-a17158
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spelling doaj-c0fe89fcc2914b48890012ae05c161662020-11-24T22:43:45ZengDove Medical PressInternational Journal of Nanomedicine1178-20132014-06-012014Issue 12905291717158Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticlesZhou JZhang JGao W Jie Zhou,1,* Jian Zhang,2,* Wenxi Gao11Department of Urology, Hubei Hospital of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA*These authors contributed equally to this workAbstract: The stability of enzyme-conjugated magnetic iron oxide nanoparticles in plasma is of great importance for in vivo delivery of the conjugated enzyme. In this study, ß-glucosidase was conjugated on aminated magnetic iron oxide nanoparticles using the glutaraldehyde method (ß-Glu-MNP), and further PEGylated via N-hydroxysuccinimide chemistry. The PEG-modified, ß-glucosidase-immobilized magnetic iron oxide nanoparticles (PEG-ß-Glu-MNPs) were characterized by hydrodynamic diameter distribution, zeta potential, Fourier transform infrared spectroscopy, transmission electron microscopy, and a superconducting quantum interference device. The results showed that the multidomain structure and magnetization properties of these nanoparticles were conserved well throughout the synthesis steps, with an expected diameter increase and zeta potential shifts. The Michaelis constant was calculated to evaluate the activity of conjugated ß-glucosidase on the magnetic iron oxide nanoparticles, indicating 73.0% and 65.4% of enzyme activity remaining for ß-Glu-MNP and PEG-ß-Glu-MNP, respectively. Both magnetophoretic mobility analysis and pharmacokinetics showed improved in vitro/in vivo stability of PEG-ß-Glu-MNP compared with ß-Glu-MNP. In vivo magnetic targeting of PEG-ß-Glu-MNP was confirmed by magnetic resonance imaging and electron spin resonance analysis in a mouse model of subcutaneous 9L-glioma. Satisfactory accumulation of PEG-ß-Glu-MNP in tumor tissue was successfully achieved, with an iron content of 627±45 nmol Fe/g tissue and ß-glucosidase activity of 32.2±8.0 mU/g tissue.Keywords: ß-glucosidase, enzyme/prodrug therapy, magnetic nanoparticles, magnetic targeting, 9L-gliomahttp://www.dovepress.com/enhanced-and-selective-delivery-of-enzyme-therapy-to-9l-glioma-tumor-v-a17158
collection DOAJ
language English
format Article
sources DOAJ
author Zhou J
Zhang J
Gao W
spellingShingle Zhou J
Zhang J
Gao W
Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles
International Journal of Nanomedicine
author_facet Zhou J
Zhang J
Gao W
author_sort Zhou J
title Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles
title_short Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles
title_full Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles
title_fullStr Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles
title_full_unstemmed Enhanced and selective delivery of enzyme therapy to 9L-glioma tumor via magnetic targeting of PEG-modified, ß-glucosidase- conjugated iron oxide nanoparticles
title_sort enhanced and selective delivery of enzyme therapy to 9l-glioma tumor via magnetic targeting of peg-modified, ß-glucosidase- conjugated iron oxide nanoparticles
publisher Dove Medical Press
series International Journal of Nanomedicine
issn 1178-2013
publishDate 2014-06-01
description Jie Zhou,1,* Jian Zhang,2,* Wenxi Gao11Department of Urology, Hubei Hospital of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA*These authors contributed equally to this workAbstract: The stability of enzyme-conjugated magnetic iron oxide nanoparticles in plasma is of great importance for in vivo delivery of the conjugated enzyme. In this study, ß-glucosidase was conjugated on aminated magnetic iron oxide nanoparticles using the glutaraldehyde method (ß-Glu-MNP), and further PEGylated via N-hydroxysuccinimide chemistry. The PEG-modified, ß-glucosidase-immobilized magnetic iron oxide nanoparticles (PEG-ß-Glu-MNPs) were characterized by hydrodynamic diameter distribution, zeta potential, Fourier transform infrared spectroscopy, transmission electron microscopy, and a superconducting quantum interference device. The results showed that the multidomain structure and magnetization properties of these nanoparticles were conserved well throughout the synthesis steps, with an expected diameter increase and zeta potential shifts. The Michaelis constant was calculated to evaluate the activity of conjugated ß-glucosidase on the magnetic iron oxide nanoparticles, indicating 73.0% and 65.4% of enzyme activity remaining for ß-Glu-MNP and PEG-ß-Glu-MNP, respectively. Both magnetophoretic mobility analysis and pharmacokinetics showed improved in vitro/in vivo stability of PEG-ß-Glu-MNP compared with ß-Glu-MNP. In vivo magnetic targeting of PEG-ß-Glu-MNP was confirmed by magnetic resonance imaging and electron spin resonance analysis in a mouse model of subcutaneous 9L-glioma. Satisfactory accumulation of PEG-ß-Glu-MNP in tumor tissue was successfully achieved, with an iron content of 627±45 nmol Fe/g tissue and ß-glucosidase activity of 32.2±8.0 mU/g tissue.Keywords: ß-glucosidase, enzyme/prodrug therapy, magnetic nanoparticles, magnetic targeting, 9L-glioma
url http://www.dovepress.com/enhanced-and-selective-delivery-of-enzyme-therapy-to-9l-glioma-tumor-v-a17158
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