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

Zhou J, Zhang J, Gao W - Int J Nanomedicine (2014)

Bottom Line: 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.Both magnetophoretic mobility analysis and pharmacokinetics showed improved in vitro/in vivo stability of PEG-β-Glu-MNP compared with β-Glu-MNP.In vivo magnetic targeting of PEG-β-Glu-MNP was confirmed by magnetic resonance imaging and electron spin resonance analysis in a mouse model of subcutaneous 9L-glioma.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Hubei Hospital of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.

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, β-glucosidase was conjugated on aminated magnetic iron oxide nanoparticles using the glutaraldehyde method (β-Glu-MNP), and further PEGylated via N-hydroxysuccinimide chemistry. The PEG-modified, β-glucosidase-immobilized magnetic iron oxide nanoparticles (PEG-β-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 β-glucosidase on the magnetic iron oxide nanoparticles, indicating 73.0% and 65.4% of enzyme activity remaining for β-Glu-MNP and PEG-β-Glu-MNP, respectively. Both magnetophoretic mobility analysis and pharmacokinetics showed improved in vitro/in vivo stability of PEG-β-Glu-MNP compared with β-Glu-MNP. In vivo magnetic targeting of PEG-β-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-β-Glu-MNP in tumor tissue was successfully achieved, with an iron content of 627±45 nmol Fe/g tissue and β-glucosidase activity of 32.2±8.0 mU/g tissue.

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Measurement of iron content in targeted or nontargeted tumor tissue of mice administered with D-MNP, β-Glu-MNP, or PEG-β-Glu-MNP.Abbreviations: D-MNP, MAG-D magnetic nanoparticles; PEG, poly(ethylene glycol); β-Glu, β-glucosidase; MNP, magnetic nanoparticles.
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f8-ijn-9-2905: Measurement of iron content in targeted or nontargeted tumor tissue of mice administered with D-MNP, β-Glu-MNP, or PEG-β-Glu-MNP.Abbreviations: D-MNP, MAG-D magnetic nanoparticles; PEG, poly(ethylene glycol); β-Glu, β-glucosidase; MNP, magnetic nanoparticles.

Mentions: All MRI results were further quantified by ex vivo analysis of MNP concentrations in excised tumor tissues taken one hour post-MNP administration. As shown in Figure 8, higher MNP concentrations were detected in tumor lesions from mice administered PEG-β-Glu-MNP (627±45 nmol Fe/g tissue, 8.5-fold higher) or β-Glu-MNP (289±58 nmol Fe/g tissue, 3.9-fold higher), compared with those injected with D-MNP (74±30 nmol Fe/g tissue). Moreover, magnetic targeting resulted in significantly greater accumulation of all three types of MNP in tumors than those of their nontargeted counterparts (8.7-fold lower for PEG-β-Glu-MNP at 71.8±5.1 nmol Fe/g tissue; 14.5-fold lower for β-Glu-MNP at 20.0±5.0 nmol Fe/g tissue; and 8.0-fold lower for D-MNP at 9.2±3.2 nmol Fe/g tissue).


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

Zhou J, Zhang J, Gao W - Int J Nanomedicine (2014)

Measurement of iron content in targeted or nontargeted tumor tissue of mice administered with D-MNP, β-Glu-MNP, or PEG-β-Glu-MNP.Abbreviations: D-MNP, MAG-D magnetic nanoparticles; PEG, poly(ethylene glycol); β-Glu, β-glucosidase; MNP, magnetic nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061166&req=5

f8-ijn-9-2905: Measurement of iron content in targeted or nontargeted tumor tissue of mice administered with D-MNP, β-Glu-MNP, or PEG-β-Glu-MNP.Abbreviations: D-MNP, MAG-D magnetic nanoparticles; PEG, poly(ethylene glycol); β-Glu, β-glucosidase; MNP, magnetic nanoparticles.
Mentions: All MRI results were further quantified by ex vivo analysis of MNP concentrations in excised tumor tissues taken one hour post-MNP administration. As shown in Figure 8, higher MNP concentrations were detected in tumor lesions from mice administered PEG-β-Glu-MNP (627±45 nmol Fe/g tissue, 8.5-fold higher) or β-Glu-MNP (289±58 nmol Fe/g tissue, 3.9-fold higher), compared with those injected with D-MNP (74±30 nmol Fe/g tissue). Moreover, magnetic targeting resulted in significantly greater accumulation of all three types of MNP in tumors than those of their nontargeted counterparts (8.7-fold lower for PEG-β-Glu-MNP at 71.8±5.1 nmol Fe/g tissue; 14.5-fold lower for β-Glu-MNP at 20.0±5.0 nmol Fe/g tissue; and 8.0-fold lower for D-MNP at 9.2±3.2 nmol Fe/g tissue).

Bottom Line: 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.Both magnetophoretic mobility analysis and pharmacokinetics showed improved in vitro/in vivo stability of PEG-β-Glu-MNP compared with β-Glu-MNP.In vivo magnetic targeting of PEG-β-Glu-MNP was confirmed by magnetic resonance imaging and electron spin resonance analysis in a mouse model of subcutaneous 9L-glioma.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Hubei Hospital of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.

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, β-glucosidase was conjugated on aminated magnetic iron oxide nanoparticles using the glutaraldehyde method (β-Glu-MNP), and further PEGylated via N-hydroxysuccinimide chemistry. The PEG-modified, β-glucosidase-immobilized magnetic iron oxide nanoparticles (PEG-β-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 β-glucosidase on the magnetic iron oxide nanoparticles, indicating 73.0% and 65.4% of enzyme activity remaining for β-Glu-MNP and PEG-β-Glu-MNP, respectively. Both magnetophoretic mobility analysis and pharmacokinetics showed improved in vitro/in vivo stability of PEG-β-Glu-MNP compared with β-Glu-MNP. In vivo magnetic targeting of PEG-β-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-β-Glu-MNP in tumor tissue was successfully achieved, with an iron content of 627±45 nmol Fe/g tissue and β-glucosidase activity of 32.2±8.0 mU/g tissue.

Show MeSH
Related in: MedlinePlus