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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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Fourier transform infrared spectra of PEG (black), β-Glu (red), D-MNP (green), β-Glu-MNP (azure), and PEG-β-Glu-MNP (blue).Abbreviations: PEG, poly(ethylene glycol); β-Glu, β-glucosidase; MNP, magnetic nanoparticles; D-MNP, MAG-D magnetic nanoparticles.
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f2-ijn-9-2905: Fourier transform infrared spectra of PEG (black), β-Glu (red), D-MNP (green), β-Glu-MNP (azure), and PEG-β-Glu-MNP (blue).Abbreviations: PEG, poly(ethylene glycol); β-Glu, β-glucosidase; MNP, magnetic nanoparticles; D-MNP, MAG-D magnetic nanoparticles.

Mentions: Figure 2 shows the Fourier transform infrared spectra for PEG, β-glucosidase, D-MNP, PEG-β-Glu-MNP, and β-Glu-MNP. The infrared spectra for PEG and PEG-β-Glu-MNP showed the hallmark absorption peak of C-O-C ether bond stretching vibrations (at 1,100 cm−1), indicating correct attachment of the PEG moieties of PEG-β-Glu-MNP. Further, the peaks at 2,934.8 cm−1 and 1,543.1 cm−1 shown in the infrared spectra of free β-glucosidase, PEG-β-Glu-MNP, and β-Glu-MNP are assigned to the amide bonds of β-glucosidase, confirming successful conjugation of β-glucosidase on both types of MNP. Compared with the infrared spectrum of D-MNP, the presence of new absorption peaks in the spectra of PEG-β-Glu-MNP (1,100 cm−1, 2,934.8 cm−1, and 1,543.1 cm−1) and β-Glu-MNP (2,934.8 cm−1 and 1,543.1 cm−1) indicated correct synthesis of β-Glu-MNP and PEG-β-Glu-MNP.


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)

Fourier transform infrared spectra of PEG (black), β-Glu (red), D-MNP (green), β-Glu-MNP (azure), and PEG-β-Glu-MNP (blue).Abbreviations: PEG, poly(ethylene glycol); β-Glu, β-glucosidase; MNP, magnetic nanoparticles; D-MNP, MAG-D magnetic nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-9-2905: Fourier transform infrared spectra of PEG (black), β-Glu (red), D-MNP (green), β-Glu-MNP (azure), and PEG-β-Glu-MNP (blue).Abbreviations: PEG, poly(ethylene glycol); β-Glu, β-glucosidase; MNP, magnetic nanoparticles; D-MNP, MAG-D magnetic nanoparticles.
Mentions: Figure 2 shows the Fourier transform infrared spectra for PEG, β-glucosidase, D-MNP, PEG-β-Glu-MNP, and β-Glu-MNP. The infrared spectra for PEG and PEG-β-Glu-MNP showed the hallmark absorption peak of C-O-C ether bond stretching vibrations (at 1,100 cm−1), indicating correct attachment of the PEG moieties of PEG-β-Glu-MNP. Further, the peaks at 2,934.8 cm−1 and 1,543.1 cm−1 shown in the infrared spectra of free β-glucosidase, PEG-β-Glu-MNP, and β-Glu-MNP are assigned to the amide bonds of β-glucosidase, confirming successful conjugation of β-glucosidase on both types of MNP. Compared with the infrared spectrum of D-MNP, the presence of new absorption peaks in the spectra of PEG-β-Glu-MNP (1,100 cm−1, 2,934.8 cm−1, and 1,543.1 cm−1) and β-Glu-MNP (2,934.8 cm−1 and 1,543.1 cm−1) indicated correct synthesis of β-Glu-MNP and PEG-β-Glu-MNP.

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