Gum Arabic-Coated Magnetic Nanoparticles for Potential Application in Simultaneous Magnetic Targeting and Tumor Imaging

Magnetic iron oxide nanoparticles (MNP) coated with gum arabic (GA), a biocompatible phytochemical glycoprotein widely used in the food industry, were successfully synthesized and characterized. GA-coated MNP (GA-MNP) displayed a narrow hydrodynamic particle size distribution averaging about 100 nm; a GA content of 15.6% by dry weight; a saturation magnetization of 93.1 emu/g Fe; and a superparamagnetic behavior essential for most magnetic-mediated applications. The GA coating offers two major benefits: it both enhances colloidal stability and provides reactive functional groups suitable for coupling of bioactive compounds. In vitro results showed that GA-MNP possessed a superior stability upon storage in aqueous media when compared to commercial MNP products currently used in magnetic resonance imaging (MRI). In addition, significant cellular uptake of GA-MNP was evaluated in 9L glioma cells by electron spin resonance (ESR) spectroscopy, fluorescence microscopy, and MRI analyses. Based on these findings, it was hypothesized that GA-MNP might be utilized as a MRI-visible drug carrier in achieving both magnetic tumor targeting and intracellular drug delivery. Indeed, preliminary in vivo investigations validate this clinical potential. MRI visually confirmed the accumulation of GA-MNP at the tumor site following intravenous administration to rats harboring 9L glioma tumors under the application of an external magnetic field. ESR spectroscopy quantitatively revealed a 12-fold increase in GA-MNP accumulation in excised tumors when compared to contralateral normal brain. Overall, the results presented show promise that GA-MNP could potentially be employed to achieve simultaneous tumor imaging and targeted intra-tumoral drug delivery.

[1]  Yongzhuo Huang,et al.  PEGylated synthetic surfactant vesicles (Niosomes): novel carriers for oligonucleotides , 2008, Journal of materials science. Materials in medicine.

[2]  M. Seki,et al.  Magnetic properties of ultrafine ferrite particles , 1987 .

[3]  Christian Bergemann,et al.  Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. , 2008, Biomaterials.

[4]  E. E. Carpenter,et al.  Chemically prepared magnetic nanoparticles , 2004 .

[5]  M. Muhammed,et al.  Synthesis and characterization of surfactant-coated superparamagnetic monodispersed iron oxide nanoparticles , 2001 .

[6]  Yongzhuo Huang,et al.  Glioma selectivity of magnetically targeted nanoparticles: a role of abnormal tumor hydrodynamics. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[7]  Philippe Robert,et al.  Recent advances in iron oxide nanocrystal technology for medical imaging. , 2006, Advanced drug delivery reviews.

[8]  Raghuraman Kannan,et al.  Nanocompatible chemistry toward fabrication of target-specific gold nanoparticles. , 2006, Journal of the American Chemical Society.

[9]  J. T. Mayo,et al.  Low-Field Magnetic Separation of Monodisperse Fe3O4 Nanocrystals , 2006, Science.

[10]  Shan X. Wang,et al.  Synthesis and characterization of PVP-coated large core iron oxide nanoparticles as an MRI contrast agent , 2008, Nanotechnology.

[11]  David J. Robertson,et al.  Gum arabic as a phytochemical construct for the stabilization of gold nanoparticles: in vivo pharmacokinetics and X-ray-contrast-imaging studies. , 2007, Small.

[12]  Chung-Yuan Mou,et al.  Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. , 2007, Nano letters.

[13]  S. Banerjee,et al.  Multifunctional pH-sensitive magnetic nanoparticles for simultaneous imaging, sensing and targeted intracellular anticancer drug delivery , 2008, Nanotechnology.

[14]  Hongjuan Ma,et al.  Facile synthesis of polymer-enveloped ultrasmall superparamagnetic iron oxide for magnetic resonance imaging , 2007, Nanotechnology.

[15]  T. Chenevert,et al.  Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: an MRI study. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Xiaobin Fan,et al.  Isolation of carbon nanohorn assemblies and their potential for intracellular delivery , 2007 .

[17]  J. Santamaría,et al.  Magnetic nanoparticles for drug delivery , 2007 .

[18]  É. Duguet,et al.  Magnetic nanoparticle design for medical diagnosis and therapy , 2004 .

[19]  Jinwoo Cheon,et al.  Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. , 2005, Journal of the American Chemical Society.

[20]  M. Gee,et al.  Zeta potentials of gum arabic stabilised oil in water emulsions , 1999 .

[21]  G. Phillips,et al.  A review of recent developments on the regulatory, structural and functional aspects of gum arabic. , 1997 .

[22]  Alke Petri-Fink,et al.  Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): colloidal stability, cytotoxicity, and cellular uptake studies. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[23]  R Weissleder,et al.  Superparamagnetic iron oxide: pharmacokinetics and toxicity. , 1989, AJR. American journal of roentgenology.