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已发表论文
通过 PEG 修饰的、β-葡萄糖苷酶-偶联氧化铁纳米颗粒的磁性靶向将酶治疗物递送至 9L-胶质肿瘤的增强与选择性研究
Authors Zhou J, Zhang J, Gao W
Published Date June 2014 Volume 2014:9(1) Pages 2905—2917
DOI http://dx.doi.org/10.2147/IJN.S59556
Received 21 December 2013, Accepted 17 February 2014, Published 10 June 2014
Abstract: 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
Keywords: ß-glucosidase, enzyme/prodrug therapy, magnetic nanoparticles, magnetic targeting, 9L-glioma
