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Int J Nanomedicine. 2013;8:3383-94. doi: 10.2147/IJN.S44829. Epub 2013 Sep 24.

Conjugation of glucosamine with Gd3+-based nanoporous silica using a heterobifunctional ANB-NOS crosslinker for imaging of cancer cells.

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  • 1Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

BACKGROUND:

The aim of this study was to synthesize Gd(3+)-based silica nanoparticles that conjugate easily with glucosamine and to investigate their use as a nanoprobe for detection of human fibrosarcoma cells.

METHODS:

Based on the structure of the 2-fluoro-2-deoxy-D-glucose molecule ((18)FDG), a new compound consisting of D-glucose (1.1 nm) was conjugated with a Gd(3+)-based mesoporous silica nanoparticle using an N-5-azido-2-nitrobenzoyloxy succinimide (ANB-NOS) crosslinker The contrast agent obtained was characterized using a variety of methods, including Fourier transform infrared spectroscopy, nitrogen physisorption, thermogravimetric analysis, scanning and transmission electron microscopy, and inductively coupled plasma atomic emission spectrometry (ICP-AES). In vitro studies included cell toxicity, apoptosis, tumor necrosis factor-alpha, and hexokinase assays, and in vivo tests consisted of evaluation of blood glucose levels using the contrast compound and tumor imaging. The cellular uptake study was validated using ICP-AES. Magnetic resonance relaxivity of the contrast agent was determined using a 1.5 Tesla scanner.

RESULTS:

ANB-NOS was found to be the preferred linker for attaching glucosamine onto the surface of the mesoporous silica nanospheres. The r1 relaxivity for the nanoparticles was 17.70 mM(-1)s(-1) per Gd(3+) ion, which is 4.4 times larger than that for Magnevist® (r1 approximately 4 mM(-1)s(-1) per Gd(3+) ion). The compound showed suitable cellular uptake (75.6% ± 2.01%) without any appreciable cytotoxicity.

CONCLUSION:

Our results suggest that covalently attaching glucosamine molecules to mesoporous silica nanoparticles enables effective targeted delivery of a contrast agent.

KEYWORDS:

N-5-azido-2-nitrobenzoyloxy succinimide; gadolinium; glucosamine; magnetic resonance imaging; mesoporous silica nanospheres; photoactivation

PMID:
24101868
[PubMed - indexed for MEDLINE]
PMCID:
PMC3790884
Free PMC Article
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