title: Magnetic tumor targeting of β-glucosidase immobilized iron oxide nanoparticles.
abstract: Directed enzyme/prodrug therapy (DEPT) has promising application for cancer therapy. However, most current DEPT strategies face shortcomings such as the loss of enzyme activity during preparation, low delivery and transduction efficiency in vivo and difficultly of monitoring. In this study, a novel magnetic directed enzyme/prodrug therapy (MDEPT) was set up by conjugating β-glucosidase (β-Glu) to aminated, starch-coated, iron oxide magnetic iron oxide nanoparticles (MNPs), abbreviated as β-Glu-MNP, using glutaraldehyde as the crosslinker. This β-Glu-MNP was then characterized in detail by size distribution, zeta potential, FTIR spectra, TEM, SQUID and magnetophoretic mobility analysis. Compared to free enzyme, the conjugated β-Glu on MNPs retained 85.54% ± 6.9% relative activity and showed much better temperature stability. The animal study results showed that β-Glu-MNP displays preferable pharmacokinetics characteristics in relation to MNPs. With an adscititious magnetic field on the surface of a tumor, a significant quantity of β-Glu-MNP was selectively delivered into a subcutaneous tumor of a glioma-bearing mouse. Remarkably, the enzyme activity of the delivered β-Glu in tumor lesions showed as high as 20.123±5.022 mU g(-1) tissue with 2.14 of tumor/non-tumor β-Glu activity.
authors: Department of Urology, The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, People's Republic of China. zhoujieuser@163.com
authors: Jie
authors: J
authors: Zhou
authors: Jian
authors: J
authors: Zhang
authors: Allan E
authors: AE
authors: David
authors: Victor C
authors: VC
authors: Yang
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D004800:Enzymes, Immobilized / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry*; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging; D008280:Magnetics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D001617:beta-Glucosidase / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D004800:Enzymes, Immobilized; D005290:Ferric Compounds; C000499:ferric oxide; D001617:beta-Glucosidase
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