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Characterization of fluorescent iron nanoparticles—candidates for multimodal tracking of neuronal transport

1 Department of Materials Science and Engineering, University of Maryland College Park, 20742, MD, USA
2 Department of Chemistry and Biochemistry, University of Maryland, College Park, 20742, MD, USA
3 Fischell Department of Bioengineering, University of Maryland, College Park, 20742, MD, USA
4 Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, 20742, MD, USA
5 Departments of Orthopedic Surgery and Bioengineering, University of California, San Diego, 92093, La Jolla, CA, USA

Topical Section: Cell and Tissue Engineering

Magnetic nanoparticles were coated with either dextran or polyacrylic acid (PAA), and compared as potential traceable carriers for targeted intraneuronal therapeutics. Nanoparticles were fabricated using a chemical reduction method and their number mean diameter, aggregation, surface chemistry, crystal structure and magnetic properties were characterized. The crystalline core of the dextran-coated nanoparticles was Fe3O4, while the PAA-coated sample had an iron core. The dextran-coated iron oxide nanoparticles (DIONs) and PAA-coated iron nanoparticles (PAINs) were both stable and had a similar mean diameter of less than 10 nm. However, morphologically, the PAINs were well dispersed, while the DIONs aggregated. DIONs exhibited the presence of hysteresis and ferromagnetic properties due to aggregation, while PAINs displayed superparamagnetic behavior. Surface chemistry analysis after 2 weeks of being exposed to air indicated that DIONs oxidized to Fe2O3, while PAINs were composed of a metallic Fe core and a mixed oxidation state shell. Based on these analyses, we concluded that PAINs are stronger candidates for examining axonal transport, since they were less prone to aggregation, offered a stronger magnetic signal, and were less oxidized. Neurotoxicity analysis of PAINs revealed that no significant toxicity was observed compared to negative controls for concentrations up to 1 mg/ml, thus further indicating their potential utility for biological applications. Finally, we successfully conjugated PAINs to a fluorophore, rhodamine 110 chloride, through a simple two-step reaction, demonstrating the feasibility of functionalizing PAINs. This study suggests that PAINs should be further evaluated as a candidate technology for intraneuronal diagnostics and therapy.
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Keywords nanoparticles; axonal transport; neuron; polyacrylic acid; dextran; superparamagnetic; functionalized; fluorescence

Citation: Olatunji Godo, Karen Gaskell, Gunja K. Pathak, Christina R. Kyrtsos, Sheryl H. Ehrman, Sameer B. Shah. Characterization of fluorescent iron nanoparticles—candidates for multimodal tracking of neuronal transport. AIMS Bioengineering, 2016, 3(3): 362-378. doi: 10.3934/bioeng.2016.3.362


  • 1. Goldstein LS, Yang Z (2000) Microtubule-based transport systems in neurons: the roles of kinesins and dyneins. Annu Rev Neurosci 23: 39–71.    
  • 2. Hirokawa N, Takemura R (2004) Molecular motors in neuronal development, intracellular transport and diseases. Curr Opin Neurobiol 14: 564–573.    
  • 3. Duncan JE, Goldstein LS (2006) The genetics of axonal transport and axonal transport disorders. PLoS Genet 2: e124.    
  • 4. Chevalier-Larsen E, Holzbaur EL (2006) Axonal transport and neurodegenerative disease. Biochim Biophys Acta 1762: 1094–1108.    
  • 5. Misgeld T, Kerschensteiner M, Bareyre FM, et al. (2007) Imaging axonal transport of mitochondria in vivo. Nat Methods 4: 559–561.    
  • 6. Kaether C, Skehel P, Dotti CG (2000) Axonal membrane proteins are transported in distinct carriers: a two-color video microscopy study in cultured hippocampal neurons. Mol Biol Cell 11: 1213–1224.    
  • 7. Enochs WS, Schaffer B, Bhide PG, et al. (1993) MR imaging of slow axonal transport in vivo. Exp Neurol 123: 235–242.    
  • 8. Petropoulos AE, Schaffer BK, Cheney ML, et al. (1995) MR imaging of neuronal transport in the guinea pig facial nerve: initial findings. Acta Otolaryngol 115: 512–516.    
  • 9. Filler AG, Bell BA (1992) Axonal transport, imaging, and the diagnosis of nerve compression. Br J Neurosurg 6: 293–295.    
  • 10. Thuen M, Berry M, Pedersen TB, et al. (2008) Manganese-enhanced MRI of the rat visual pathway: acute neural toxicity, contrast enhancement, axon resolution, axonal transport, and clearance of Mn2+. J Magn Reson Imaging 28: 855–865.    
  • 11. Hussain SM, Javorina AK, Schrand AM, et al. (2006) The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. Toxicol Sci 92: 456–463.    
  • 12. Pisanic TR 2nd, Blackwell JD, Shubayev VI, et al. (2007) Nanotoxicity of iron oxide nanoparticle internalization in growing neurons. Biomaterials 28: 2572–2581.    
  • 13. Couillard-Despres S, Finkl R, Winner B, et al. (2008) In vivo optical imaging of neurogenesis: watching new neurons in the intact brain. Mol Imaging 7: 28–34.
  • 14. Choi JS, Park JC, Nah H, et al. (2008) A hybrid nanoparticle probe for dual-modality positron emission tomography and magnetic resonance imaging. Angew Chem Int Ed Engl 47: 6259–6262.    
  • 15. Focke A, Schwarz S, Foerschler A, et al. (2008) Labeling of human neural precursor cells using ferromagnetic nanoparticles. Magn Reson Med 60: 1321–1328.    
  • 16. Townsend SA, Evrony GD, Gu FX, et al. (2007) Tetanus toxin C fragment-conjugated nanoparticles for targeted drug delivery to neurons. Biomaterials 28: 5176–5184.    
  • 17. Rivet CJ, Yuan Y, Borca-Tasciuc DA, et al. (2012) Altering iron oxide nanoparticle surface properties induce cortical neuron cytotoxicity. Chem Res Toxicol 25: 153–161.    
  • 18. Filler AG (1994) Axonal transport and MR imaging: prospects for contrast agent development. J Magn Reson Imaging 4: 259–267.    
  • 19. Huang KC, Ehrman SH (2007) Synthesis of iron nanoparticles via chemical reduction with palladium ion seeds. Langmuir 23: 1419–1426.    
  • 20. Bean CP, Jacobs IS (1956) Magnetic granulometry and super-paramagnetism. J Appl Phys 27: 1448–1452.    
  • 21. Chantrell RW, Popplewell J, Charles SW (1978) Measurements of particle-size distribution parameters in ferrofluids. Ieee T Magn 14: 975–977.    
  • 22. Yatsuya S, Hayashi T, Akoh H, et al. (1978) Magnetic-properties of extremely fine particles of iron prepared by vacuum evaporation on running oil substrate. Jpn J Appl Phys 17: 355–359.
  • 23. Cullity BD (1972) Introduction to magnetic materials. New York: Addison-Wiley.
  • 24. Burke NAD, Stover HDH, Dawson FP (2002) Magnetic nanocomposites: Preparation and characterization of polymer-coated iron nanoparticles. Chem Mater 14: 4752–4761.    
  • 25. Frazier RA, Davies MC, Matthijs G, et al. (1997) In situ surface plasmon resonance analysis of dextran monolayer degradation by dextranase. Langmuir 13: 7115–7120.    
  • 26. Lan Y, Cheng C, Zhang SZ, et al. (2011) Plasma-induced Styrene Grafting onto the Surface of Polytetrafluoroethylene Powder for Proton Exchange Membrane Application. Plasma Sci Technol 13: 604–607.    
  • 27. Shanmugam S, Viswanathan B, Varadarajan TK (2006) A novel single step chemical route for noble metal nanoparticles embedded organic-inorganic composite films. Mater Chem Phys 95: 51–55.    
  • 28. Jung HI, Huh SH, Oh SJ, et al. (1999) Oxidation enthalpy of 6 nm Fe clusters. J Korean Phys Soc 35: 265–267.
  • 29. Simeonidis K, Mourdikoudis S, Tsiaoussis I, et al. (2007) Oxidation process of Fe nanoparticles. Mod Phys Lett B 21: 1143–1151.    
  • 30. Morales MP, Bomati-Miguel O, de Alejo RP, et al. (2003) Contrast agents for MRI based on iron oxide nanoparticles prepared by laser pyrolysis. J Magn Magn Mater 266: 102–109.    
  • 31. Hong RY, Li JH, Qu JM, et al. (2009) Preparation and characterization of magnetite/dextran nanocomposite used as a precursor of magnetic fluid. Chem Eng J 150: 572–580.    
  • 32. Lin CL, Lee CF, Chiu WY (2005) Preparation and properties of poly(acrylic acid) oligomer stabilized superparamagnetic ferrofluid. J Colloid Interf Sci 291: 411–420.    
  • 33. Lin MM, Li SH, Kim HH, et al. (2010) Complete separation of magnetic nanoparticles via chemical cleavage of dextran by ethylenediamine for intracellular uptake. J Mater Chem 20: 444–447.    
  • 34. Lin JJ, Chen JS, Huang SJ, et al. (2009) Folic acid-Pluronic F127 magnetic nanoparticle clusters for combined targeting, diagnosis, and therapy applications. Biomaterials 30: 5114–5124.    
  • 35. Gupta AK, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26: 3995–4021.    
  • 36. Kuzminski M, Slawska-Waniewska A, Lachowicz HK (1999) The influence of superparamagnetic particle size distribution and ferromagnetic phase on GMR in melt spun Cu-Co granular alloys. Ieee T Magn 35: 2853–2855.    
  • 37. Yamashita T, Hayes P (2008) Analysis of XPS spectra of Fe2+ and Fe3+ ions in oxide materials. Appl Surf Sci 254: 2441–2449.    
  • 38. Barandeh F, Nguyen PL, Kumar R, et al. (2012) Organically modified silica nanoparticles are biocompatible and can be targeted to neurons in vivo. PLoS One 7: e29424.    
  • 39. Thuen M, Olsen O, Berry M, et al. (2009) Combination of Mn2+-enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve. J Magn Reson Imaging 29: 39–51.    
  • 40. Liu W, Frank JA (2008) Detection and quantification of magnetically labeled cells by cellular MRI. Eur J Radiol 70: 258–264.
  • 41. Watanabe T, Radulovic J, Spiess J, et al. (2004) In vivo 3D MRI staining of the mouse hippocampal system using intracerebral injection of MnCl2. Neuroimage 22: 860–867.    
  • 42. Gilad AA, Walczak P, McMahon MT, et al. (2008) MR tracking of transplanted cells with "positive contrast" using manganese oxide nanoparticles. Magn Reson Med 60: 1–7.    
  • 43. Hsiao JK, Tsai CP, Chung TH, et al. (2008) Mesoporous silica nanoparticles as a delivery system of gadolinium for effective human stem cell tracking. Small 4: 1445–1452.    
  • 44. Sumner JP, Shapiro EM, Maric D, et al. (2009) In vivo labeling of adult neural progenitors for MRI with micron sized particles of iron oxide: quantification of labeled cell phenotype. Neuroimage 44: 671–678.    
  • 45. Muldoon LL, Sandor M, Pinkston KE, et al. (2005) Imaging, distribution, and toxicity of superparamagnetic iron oxide magnetic resonance nanoparticles in the rat brain and intracerebral tumor. Neurosurgery 57: 785–796.
  • 46. Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4: 26–49.    
  • 47. Cosker KE, Courchesne SL, Segal RA (2008) Action in the axon: generation and transport of signaling endosomes. Curr Opin Neurobiol 18: 270–275.    
  • 48. Cui B, Wu C, Chen L, et al. (2007) One at a time, live tracking of NGF axonal transport using quantum dots. P Natl Acad Sci USA 104: 13666–13671.    
  • 49. Ha J, Lo KW, Myers KR, et al. (2008) A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes. J Cell Biol 181: 1027–1039.    
  • 50. Lenz JH, Schuchardt I, Straube A, et al. (2006) A dynein loading zone for retrograde endosome motility at microtubule plus-ends. EMBO J 25: 2275–2286.    
  • 51. Dhanikula RS, Argaw A, Bouchard JF, et al. (2008) Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability. Mol Pharm 5: 105–116.    
  • 52. Jeong YI, Seo SJ, Park IK, et al. (2005) Cellular recognition of paclitaxel-loaded polymeric nanoparticles composed of poly(gamma-benzyl L-glutamate) and poly(ethylene glycol) diblock copolymer endcapped with galactose moiety. Int J Pharm 296: 151–161.    
  • 53. Lu W, Sun Q, Wan J, et al. (2006) Cationic albumin-conjugated pegylated nanoparticles allow gene delivery into brain tumors via intravenous administration. Cancer Res 66: 11878–11887.    
  • 54. Howarth M, Takao K, Hayashi Y, et al. (2005) Targeting quantum dots to surface proteins in living cells with biotin ligase. P Natl Acad Sci USA 102: 7583–7588.    
  • 55. Zhang QZ, Zha LS, Zhang Y, et al. (2006) The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles in rats. J Drug Target 14: 281–290.    
  • 56. Slotkin JR, Chakrabarti L, Dai HN, et al. (2007) In vivo quantum dot labeling of mammalian stem and progenitor cells. Dev Dyn 236: 3393–3401.    
  • 57. Gao X, Chen J, Wu B, et al. (2008) Quantum dots bearing lectin-functionalized nanoparticles as a platform for in vivo brain imaging. Bioconjug Chem 19: 2189–2195.    
  • 58. Santra S, Yang H, Holloway PH, et al. (2005) Synthesis of water-dispersible fluorescent, radio-opaque, and paramagnetic CdS: Mn/ZnS quantum dots: a multifunctional probe for bioimaging. J Am Chem Soc 127: 1656–1657.    
  • 59. Wang J, Chen C, Liu Y, et al. (2008) Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases. Toxicol Lett 183: 72–80.    
  • 60. Tang M, Xing T, Zeng J, et al. (2008) Unmodified CdSe quantum dots induce elevation of cytoplasmic calcium levels and impairment of functional properties of sodium channels in rat primary cultured hippocampal neurons. Environ Health Persp 116: 915–922.    
  • 61. Sayes CM, Gobin AM, Ausman KD, et al. (2005) Nano-C60 cytotoxicity is due to lipid peroxidation. Biomaterials 26: 7587–7595.    
  • 62. Liu G, Hong RY, Guo L, et al. (2011) Preparation, characterization and MRI application of carboxymethyl dextran coated magnetic nanoparticles. Appl Surf Sci 257: 6711–6717.    


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Copyright Info: 2016, Sameer B. Shah, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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