Engineered Biocompatible Nanoparticles for in Vivo Imaging Applications

Iron−platinum alloy nanoparticles (FePt NPs) are extremely promising candidates for the next generation of contrast agents for magnetic resonance (MR) diagnostic imaging and MR-guided interventions, including hyperthermic ablation of solid cancers. FePt has high Curie temperature, saturation magnetic moment, magneto-crystalline anisotropy, and chemical stability. We describe the synthesis and characterization of a family of biocompatible FePt NPs suitable for biomedical applications, showing and discussing that FePt NPs can exhibit low cytotoxicity. The importance of engineering the interface of strongly magnetic NPs using a coating allowing free aqueous permeation is demonstrated to be an essential parameter in the design of new generations of diagnostic and therapeutic MRI contrast agents. We report effective cell internalization of FePt NPs and demonstrate that they can be used for cellular imaging and in vivo MRI applications. This opens the way for several future applications of FePt NPs, including regenerative medicine and stem cell therapy in addition to enhanced MR diagnostic imaging.

[1]  A. Wilson,et al.  Elements of X-ray crystallography , 1970 .

[2]  Sandra L. Schmid,et al.  Regulated portals of entry into the cell , 2003, Nature.

[3]  T. Teranishi,et al.  One-pot synthesis of large FePt nanoparticles from metal salts and their thermal stability. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[4]  A. Meijerink,et al.  On the Incorporation Mechanism of Hydrophobic Quantum Dots in Silica Spheres by a Reverse Microemulsion Method , 2008 .

[5]  Miqin Zhang,et al.  Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. , 2010, Advanced drug delivery reviews.

[6]  Bobbi K Lewis,et al.  A model of lysosomal metabolism of dextran coated superparamagnetic iron oxide (SPIO) nanoparticles: implications for cellular magnetic resonance imaging , 2005, NMR in biomedicine.

[7]  F. Kiessling.  Molecular and Cellular MR Imaging , 2007 .

[8]  Direct synthesis of Pt based L10 structured nanoparticles (invited) , 2005 .

[9]  Jerry S. H. Lee,et al.  Magnetic nanoparticles in MR imaging and drug delivery. , 2008, Advanced drug delivery reviews.

[10]  S. Maenosono,et al.  Formation Mechanism of FePt Nanoparticles Synthesized via Pyrolysis of Iron(III) Ethoxide and Platinum(II) Acetylacetonate , 2005 .

[11]  Andrew McCaskie,et al.  Nanomedicine , 2005, BMJ.

[12]  Jacob Torrejon,et al.  Multipeak ferromagnetic resonance behaviour tailored by magnetoelastic coupling in FeSiB/CoNi layered microwires , 2010 .

[13]  Bing Xu,et al.  Multifunctional yolk-shell nanoparticles: a potential MRI contrast and anticancer agent. , 2008, Journal of the American Chemical Society.

[14]  D. Astruc,et al.  Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. , 2004, Chemical reviews.

[15]  D. Djayaprawira,et al.  Towards direct synthesis of fct-FePt nanoparticles by chemical route , 2003 .

[16]  S. Maenosono,et al.  Theoretical assessment of FePt nanoparticles as heating elements for magnetic hyperthermia , 2006, IEEE Transactions on Magnetics.

[17]  Sungho Jin,et al.  Magnetic nanoparticles for theragnostics. , 2009, Advanced drug delivery reviews.

[18]  Bing Xu,et al.  Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications. , 2009, Accounts of chemical research.

[19]  Igor L. Medintz,et al.  Polyethylene glycol-based bidentate ligands to enhance quantum dot and gold nanoparticle stability in biological media , 2009, Nature Protocols.

[20]  B. Korgel,et al.  Synthesis and magnetic properties of silica-coated FePt nanocrystals. , 2006, The journal of physical chemistry. B.

[21]  John S. O. Evans,et al.  A synthetic route to size-controlled fcc and fct FePt nanoparticles. , 2005, Journal of the American Chemical Society.

[22]  Jeff W M Bulte,et al.  Iron oxide MR contrast agents for molecular and cellular imaging , 2004, NMR in biomedicine.

[23]  Bing Xu,et al.  Applications of nanomaterials inside cells , 2009 .

[24]  R. Schultz,et al.  Infrared absorption spectroscopy. , 1971, American Industrial Hygiene Association journal.

[25]  R Weissleder,et al.  High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. , 1999, Bioconjugate chemistry.

[26]  Bing Xu,et al.  Using biofunctional magnetic nanoparticles to capture gram-negative bacteria at an ultra-low concentration. , 2003, Chemical communications.

[27]  Alfred Cuschieri,et al.  Rapid and efficient cell labeling with a MRI contrast agent by electroporation in the presence of protamine sulfate. , 2009, Nanomedicine.

[28]  T. Skotland,et al.  In vitro stability analyses as a model for metabolism of ferromagnetic particles (Clariscan), a contrast agent for magnetic resonance imaging. , 2002, Journal of pharmaceutical and biomedical analysis.

[29]  Q. Pankhurst,et al.  Applications of magnetic nanoparticles in biomedicine , 2003 .

[30]  Shouheng Sun,et al.  Recent Advances in Chemical Synthesis, Self‐Assembly, and Applications of FePt Nanoparticles , 2006 .

[31]  R. Crichton,et al.  Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells. , 2002, Journal of inorganic biochemistry.

[32]  Bing Xu,et al.  FePt@CoS(2) yolk-shell nanocrystals as a potent agent to kill HeLa cells. , 2007, Journal of the American Chemical Society.

[33]  Nastassja A. Lewinski,et al.  Cytotoxicity of nanoparticles. , 2008, Small.

[34]  Taeghwan Hyeon,et al.  Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. , 2009, Chemical Society reviews.

[35]  K. Landfester,et al.  Uptake mechanism of oppositely charged fluorescent nanoparticles in HeLa cells. , 2008, Macromolecular bioscience.

[36]  J. S. Evans,et al.  SYNTHESIS OF SIZE-CONTROLLED FCC AND FCT FEPT NANOPARTICLES , 2006 .

[37]  Heather Kalish,et al.  Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. , 2003, Radiology.

[38]  E. Bilensoy.  Cationic nanoparticles for cancer therapy , 2010, Expert opinion on drug delivery.

[39]  M. Dobrovolskaia,et al.  Immunological properties of engineered nanomaterials , 2007, Nature Nanotechnology.

[40]  S. Maenosono,et al.  Superparamagnetic FePt nanoparticles as excellent MRI contrast agents , 2008 .

[41]  J. Liu,et al.  One-step synthesis of FePt nanoparticles with tunable size. , 2004, Journal of the American Chemical Society.

[42]  Taeghwan Hyeon,et al.  Inorganic Nanoparticles for MRI Contrast Agents , 2009 .

[43]  Alexander Petrovsky,et al.  Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture. , 2002, Bioconjugate chemistry.

[44]  S. Raoux,et al.  Silicide formation and particle size growth in high-temperature-annealed, self-assembled FePt nanoparticles , 2004 .

[45]  A. Lu,et al.  Magnetic nanoparticles: synthesis, protection, functionalization, and application. , 2007, Angewandte Chemie.

[46]  J. Liu,et al.  Size and Shape Control of Monodisperse FePt Nanoparticles , 2007 .

[47]  Sun,et al.  Monodisperse FePt nanoparticles and ferromagnetic FePt nanocrystal superlattices , 2000, Science.

[48]  A. Bose,et al.  Synthesis and Assembly of Monodisperse High‐Coercivity Silica‐Capped FePt Nanomagnets of Tunable Size, Composition, and Thermal Stability from Microemulsions , 2006 .

[49]  Younan Xia,et al.  Superparamagnetic Colloids: Controlled Synthesis and Niche Applications , 2007 .

[50]  Bing Xu,et al.  Using biofunctional magnetic nanoparticles to capture vancomycin-resistant enterococci and other gram-positive bacteria at ultralow concentration. , 2003, Journal of the American Chemical Society.

[51]  A. Cuschieri,et al.  Physicochemical properties affecting cellular uptake of carbon nanotubes. , 2010, Nanomedicine.

[52]  P. Jacobs,et al.  Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. , 1995, Magnetic resonance imaging.

[53]  Heather Kalish,et al.  Comparison of Transfection Agents in Forming Complexes with Ferumoxides, Cell Labeling Efficiency, and Cellular Viability , 2004, Molecular imaging.

[54]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[55]  Y. Samson,et al.  Core–shell structure of chemically synthesised FePt nanoparticles: a comparative study , 2007 .

[56]  Ajay Kumar Gupta,et al.  Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles. , 2005, Biomaterials.

[57]  Chenjie Xu,et al.  FePt nanoparticles as an Fe reservoir for controlled Fe release and tumor inhibition. , 2009, Journal of the American Chemical Society.

[58]  S. Maenosono,et al.  Amine-Terminated Water-Dispersible FePt Nanoparticles , 2008 .