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

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Abstract

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.

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References

  1. Arruebo M, Fernandez-Pacheco R, Ibarra MR, Santamaria J. Magnetic nanoparticles for drug delivery. Nano Today. 2007;2:22–32.

    Article  Google Scholar 

  2. Chertok B, Moffat BA, David AE, Yu FQ, Bergemann C, Ross BD, et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials. 2008;29:487–96.

    Article  PubMed  CAS  Google Scholar 

  3. Wang YXJ, Hussain SM, Krestin GP. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol. 2001;11:2319–31.

    Article  PubMed  CAS  Google Scholar 

  4. Petri-Fink A, Steitz B, Finka A, Salaklang J, Hofmann H. Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): colloidal stability, cytotoxicity, and cellular uptake studies. Eur J Pharm Biopharm. 2008;68:129–37.

    Article  PubMed  CAS  Google Scholar 

  5. Mornet S, Vasseur S, Grasset F, Duguet E. Magnetic nanoparticle design for medical diagnosis and therapy. J Mater Chem. 2004;14:2161–75.

    Article  CAS  Google Scholar 

  6. Kattumuri V, Katti K, Bhaskaran S, Boote EJ, Casteel SW, Fent GM, et al. Gum arabic as a phytochemical construct for the stabilization of gold nanoparticles: in vivo pharmacokinetics and X-ray-contrast-imaging studies. Small. 2007;3:333–41.

    Article  PubMed  CAS  Google Scholar 

  7. Islam AM, Phillips GO, Sljivo A, Snowden MJ, Williams PA. A review of recent developments on the regulatory, structural and functional aspects of gum arabic. Food Hydrocolloid. 1997;11:493–505.

    Article  CAS  Google Scholar 

  8. Jayme ML, Dunstan DE, Gee ML. Zeta potentials of gum arabic stabilised oil in water emulsions. Food Hydrocolloid. 1999;13:459–65.

    Article  CAS  Google Scholar 

  9. Kannan R, Rahing V, Cutler C, Pandrapragada R, Katti KK, Kattumuri V, et al. Nanocompatible chemistry toward fabrication of target-specific gold nanoparticles. J Am Chem Soc. 2006;128:11342–3.

    Article  PubMed  CAS  Google Scholar 

  10. Fan XB, Tan J, Zhang GL, Zhang FB. Isolation of carbon nanohorn assemblies and their potential for intracellular delivery. Nanotechnology. 2007;18:195103. doi:10.1088/0957-4484/18/19/195103.

    Article  CAS  Google Scholar 

  11. Banerjee SS, Chen DH. Multifunctional pH-sensitive magnetic nanoparticles for simultaneous imaging, sensing and targeted intracellular anticancer drug delivery. Nanotechnology. 2008;19:505104. doi:10.1088/0957-4484/19/50/505104.

    Article  Google Scholar 

  12. Kim DK, Zhang Y, Voit W, Rao KV, Muhammed M. Synthesis and characterization of surfactant-coated superparamagnetic monodispersed iron oxide nanoparticles. J Magn Magn Mater. 2001;225:30–6.

    Article  CAS  Google Scholar 

  13. Huang YZ, Chen JL, Chen XJ, Gao JQ, Liang WQ. PEGylated synthetic surfactant vesicles (Niosomes): novel carriers for oligonucleotides. J Mater Sci Mater Med. 2008;19:607–14.

    Article  PubMed  CAS  Google Scholar 

  14. Ross BD, Zhao YJ, Neal ER, Stegman LD, Ercolani M, Ben-Yoseph O, et al. Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: An MRI study. Proc Natl Acad Sci U S A. 1998;95:7012–7.

    Article  PubMed  CAS  Google Scholar 

  15. Chertok B, David AE, Huang YZ, Yang VC. Glioma selectivity of magnetically targeted nanoparticles: a role of abnormal tumor hydrodynamics. J Control Release. 2007;122:315–23.

    Article  PubMed  CAS  Google Scholar 

  16. Hong J, Xu DM, Yu JH, Gong PJ, Ma HJ, Yao SD. Facile synthesis of polymer-enveloped ultrasmall superparamagnetic iron oxide for magnetic resonance imaging. Nanotechnology. 2007;18:135608. doi:10.1088/0957-4484/18/13/135608.

    Article  CAS  Google Scholar 

  17. Sato T, Iijima T, Seki M, Inagaki N. Magnetic properties of ultrafine ferrite particles. J Magn Magn Mater. 1987;65:252–6.

    Article  CAS  Google Scholar 

  18. Willard MA, Kurihara LK, Carpenter EE, Calvin S, Harris VG. Chemically prepared magnetic nanoparticles. Int Mater Rev. 2004;49:125–70.

    Article  CAS  Google Scholar 

  19. Lee HY, Lee SH, Xu CJ, Xie J, Lee JH, Wu B, et al. Synthesis and characterization of PVP-coated large core iron oxide nanoparticles as an MRI contrast agent. Nanotechnology. 2008;19:165101.1–6. doi:10.1088/0957-4484/19/16/165101.

    Google Scholar 

  20. Jun YW, Huh YM, Choi JS, Lee JH, Song HT, Kim S, et al. Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. J Am Chem Soc. 2005;127:5732–3.

    Article  PubMed  CAS  Google Scholar 

  21. Yavuz CT, Mayo JT, Yu WW, Prakash A, Falkner JC, Yean S, et al. Low-field magnetic separation of monodisperse Fe3O4 nanocrystals. Science. 2006;314:964–7.

    Article  PubMed  Google Scholar 

  22. Corot C, Robert P, Idee JM, Port M. Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliver Rev. 2006;58:1471–504.

    Article  CAS  Google Scholar 

  23. Weissleder R, Stark DD, Engelstad BL, Bacon BR, Compton CC, White DL, et al. Superparamagnetic iron oxide: pharmacokinetics and toxicity. Am J Roentgenol. 1989;152:167–73.

    CAS  Google Scholar 

  24. Lu CW, Hung Y, Hsiao JK, Yao M, Chung TH, Lin YS, et al. Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. Nano Lett. 2007;7:149–54.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported in part by NIH R01 grants CA114612, NS066945, and the Hartwell Foundation Biomedical Research Award. In addition, this work was also partially sponsored by the World Class University (WCU) program through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology (R31-2008-000-10103-01). Lei Zhang was a recipient of the Chinese Program of Introducing Talents of Discipline to Universities, no. B06006. Victor C. Yang is currently a Principal Investigator in the Department of Molecular Medicine and Biopharmaceutical Sciences, College of Medicine/College of Pharmacy, Seoul National University, South Korea. Beata Chertok was the recipient of Fred W. Lyons Jr. and Rackham Pre-Doctoral Fellowships. Adam Cole was a recipient of a NIH Pharmacological Sciences and Bio-related Chemistry Training Program (GM007767 from NIGMS) grant and is currently an American Foundation of Pharmaceutical Education (AFPE) Pre-Doctoral Fellow.

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Authors and Affiliations

  1. Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, Tianjin University, Tianjin, 300072, China

    Lei Zhang, Jingkang Wang & Victor C. Yang

  2. School of Chemical Engineering, Tianjin University, Tianjin, 300072, China

    Lei Zhang, Jingkang Wang & Victor C. Yang

  3. Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, Michigan, 48109-1065, USA

    Lei Zhang, Faquan Yu, Adam J. Cole, Beata Chertok, Allan E. David & Victor C. Yang

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  1. Lei Zhang
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  2. Faquan Yu
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  3. Adam J. Cole
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  4. Beata Chertok
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  5. Allan E. David
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  6. Jingkang Wang
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  7. Victor C. Yang
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Correspondence to Victor C. Yang.

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Zhang, L., Yu, F., Cole, A.J. et al. Gum Arabic-Coated Magnetic Nanoparticles for Potential Application in Simultaneous Magnetic Targeting and Tumor Imaging. AAPS J 11, 693–699 (2009). https://doi.org/10.1208/s12248-009-9151-y

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  • DOI: https://doi.org/10.1208/s12248-009-9151-y

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