Synthesis of superparamagnetic nanotubes as MRI contrast agents and for cell labeling.

AIMS Magnetic nanoparticles have been studied widely as MRI contrast agents to increase the sensitivity of this technique. This work describes the synthesis and characterization of magnetic nanotubes (MNTs) as a novel MRI contrast agent. METHODS MNTs with high saturation magnetization were fabricated by the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) directly in the pores of silica nanotubes (SNTs). The MNTs were characterized by electron microscopy, superconducting quantum interference device and MRI. Preliminary studies on in vitro cytotoxicity and cell labeling were carried out. RESULTS The MNTs retained the superparamagnetic characteristics in bulk solutions with a considerably high saturation magnetization of 95 emu/gFe. The nuclear magnetic resonance (NMR) relaxivities for MNTs of 500 nm in length and of 60 nm in diameter were r(1) = 1.6 +/- 0.3 mM(-1)s(-1) and r(2) = 264 +/- 56 mM(-1)s(-1) and, for the MNTs of 2 microm in length and 70 nm in diameter, the r(1) and r(2) were 3.0 +/- 1.3 and 358 +/- 65 mM(-1)s(-1), respectively. In vitro cell labeling showed promising results with excellent labeling efficiency. No cellular toxicity was observed in vitro. CONCLUSIONS The integration of SPIONs with SNTs imparts the superparamagnetic characteristics of SPIONs onto the SNTs, creating unique magnetic nanoparticles with multifunctionality. The MNTs showed promising results as a MRI contrast agent with high NMR relaxivities, little cytotoxicity and high cell-labeling efficiency.

[1]  María del Puerto Morales,et al.  Static and dynamic magnetic properties of spherical magnetite nanoparticles , 2003 .

[2]  S. Veintemillas-Verdaguer,et al.  Fe-based nanoparticulate metallic alloys as contrast agents for magnetic resonance imaging. , 2005, Biomaterials.

[3]  S. Ammar,et al.  Magnetic properties of ultrafine cobalt ferrite particles synthesized by hydrolysis in a polyol medium , 2001 .

[4]  Sang Bok Lee,et al.  Suspension array with shape-coded silica nanotubes for multiplexed immunoassays. , 2007, Analytical chemistry.

[5]  C. R. Martin,et al.  Template-synthesized nanotubes for biotechnology and biomedical applications , 2005 .

[6]  S. Caruthers,et al.  Nanoparticles for Magnetic Resonance Imaging of Tumors , 2007 .

[7]  R. Blasberg Molecular imaging and cancer. , 2003, Molecular cancer therapeutics.

[8]  L. A. Baker,et al.  Biomaterials and Biotechnologies Based on Nanotube Membranes , 2005 .

[9]  J A Frank,et al.  Combination of transfection agents and magnetic resonance contrast agents for cellular imaging: Relationship between relaxivities, electrostatic forces, and chemical composition , 2003, Magnetic resonance in medicine.

[10]  Taeghwan Hyeon,et al.  Synthesis of highly crystalline and monodisperse maghemite nanocrystallites without a size-selection process. , 2001, Journal of the American Chemical Society.

[11]  C. R. Martin,et al.  The emerging field of nanotube biotechnology , 2003, Nature Reviews Drug Discovery.

[12]  Jean-Marie Devoisselle,et al.  Magnetic nanoparticles and their applications in medicine. , 2006, Nanomedicine.

[13]  J. Bulte,et al.  Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging. , 2004, Methods in enzymology.

[14]  Hamidreza Ghandehari,et al.  Template synthesis of multifunctional nanotubes for controlled release. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[15]  Peter van Gelderen,et al.  Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells , 2001, Nature Biotechnology.

[16]  Jung-tak Jang,et al.  Magnetic Resonance Nanoparticle Probes for Cancer Imaging , 2007 .

[17]  C. R. Martin,et al.  Corking nano test tubes by chemical self-assembly. , 2006, Journal of the American Chemical Society.

[18]  T. Hyeon,et al.  One-nanometer-scale size-controlled synthesis of monodisperse magnetic iron oxide nanoparticles. , 2005, Angewandte Chemie.

[19]  Kornelius Nielsch,et al.  Hexagonal pore arrays with a 50-420 nm interpore distance formed by self-organization in anodic alumina , 1998 .

[20]  Taro Takahashi,et al.  Isothermal compression of magnetite to 320 KB , 1974 .

[21]  Z. Wu,et al.  Synthesis and characterization of functionalized silica-coated Fe3O4 superparamagnetic nanocrystals for biological applications , 2005 .

[22]  Sabino Veintemillas-Verdaguer,et al.  Surface and Internal Spin Canting in γ-Fe2O3 Nanoparticles , 1999 .

[23]  Bobbi K Lewis,et al.  In vivo trafficking and targeted delivery of magnetically labeled stem cells. , 2004, Human gene therapy.

[24]  Jinwoo Cheon,et al.  Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling. , 2005, Journal of the American Chemical Society.

[25]  Jin-Sil Choi,et al.  In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals. , 2005, Journal of the American Chemical Society.

[26]  C. Feldmann,et al.  Polyol-Mediated Preparation of Nanoscale Oxide Particles. , 2001, Angewandte Chemie.

[27]  C. Serna,et al.  chapter 5 Synthesis, Properties and Biomedical Applications of Magnetic Nanoparticles , 2006 .

[28]  Daeyeon Lee,et al.  Heterostructured magnetic nanotubes. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[29]  C. R. Martin,et al.  Smart nanotubes for bioseparations and biocatalysis. , 2002, Journal of the American Chemical Society.

[30]  Sang Bok Lee,et al.  Shape-coded silica nanotubes for biosensing. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[31]  Sang Bok Lee,et al.  Magnetic nanotubes for magnetic-field-assisted bioseparation, biointeraction, and drug delivery. , 2005, Journal of the American Chemical Society.

[32]  Ming Zhao,et al.  Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent , 2001, Nature Medicine.

[33]  Hans Söderlund,et al.  Antibody-Based Bio-Nanotube Membranes for Enantiomeric Drug Separations , 2002, Science.

[34]  D. Discher,et al.  Shape effects of filaments versus spherical particles in flow and drug delivery. , 2007, Nature nanotechnology.

[35]  Jeff W M Bulte,et al.  Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques , 2003, Transplantation.

[36]  C. R. Martin,et al.  Template synthesized nanotubes for biomedical delivery applications. , 2006, Nanomedicine.

[37]  C. O'connor,et al.  Reactivity of 3d transition metal cations in diethylene glycol solutions. Synthesis of transition metal ferrites with the structure of discrete nanoparticles complexed with long-chain carboxylate anions. , 2002, Inorganic chemistry.

[38]  J. Frank,et al.  Color Transformation and Fluorescence of Prussian Blue–Positive Cells: Implications for Histologic Verification of Cells Labeled with Superparamagnetic Iron Oxide Nanoparticles , 2007, Molecular imaging.

[39]  Klaas Nicolay,et al.  Lipid‐based nanoparticles for contrast‐enhanced MRI and molecular imaging , 2006, NMR in biomedicine.

[40]  C. R. Martin,et al.  Smart nanotubes for biotechnology. , 2005, Current pharmaceutical biotechnology.

[41]  Victor Frenkel,et al.  Magnetic Resonance Imaging and Confocal Microscopy Studies of Magnetically Labeled Endothelial Progenitor Cells Trafficking to Sites of Tumor Angiogenesis , 2006, Stem cells.

[42]  Jon Dobson,et al.  Magnetic micro- and nano-particle-based targeting for drug and gene delivery. , 2006, Nanomedicine.

[43]  C. Serna,et al.  Synthesis, Properties and Biomedical Applications of Magnetic Nanoparticles. , 2008 .

[44]  Theresa S. Mayer,et al.  Templated Surface Sol–Gel Synthesis of SiO2 Nanotubes and SiO2‐Insulated Metal Nanowires , 2003 .

[45]  Ajay Kumar Gupta,et al.  Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. , 2005, Biomaterials.

[46]  Qing Peng,et al.  Monodisperse magnetic single-crystal ferrite microspheres. , 2005, Angewandte Chemie.

[47]  Kenji Fukuda,et al.  Ordered Metal Nanohole Arrays Made by a Two-Step Replication of Honeycomb Structures of Anodic Alumina , 1995, Science.

[48]  T. Chiles,et al.  Highly efficient molecular delivery into mammalian cells using carbon nanotube spearing , 2005, Nature Methods.

[49]  Direct observation of dipolar chains in ferrofluids in zero field using cryogenic electron microscopy , 2003 .

[50]  Controlled clustering of superparamagnetic nanoparticles using block copolymers: design of new contrast agents for magnetic resonance imaging. , 2005, Journal of the American Chemical Society.

[51]  Valérie Cabuil,et al.  Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging. , 2005, Journal of the American Chemical Society.