Magnetic nanobeads as potential contrast agents for magnetic resonance imaging.

Metal-oxo clusters have been used as building blocks to form hybrid nanomaterials and evaluated as potential MRI contrast agents. We have synthesized a biocompatible copolymer based on a water stable, nontoxic, mixed-metal-oxo cluster, Mn8Fe4O12(L)16(H2O)4, where L is acetate or vinyl benzoic acid, and styrene. The cluster alone was screened by NMR for relaxivity and was found to be a promising T2 contrast agent, with r1 = 2.3 mM(-1) s(-1) and r2 = 29.5 mM(-1) s(-1). Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. The metal-oxo cluster Mn8Fe4(VBA)16 (VBA = vinyl benzoic acid) can be copolymerized with styrene under miniemulsion conditions. Miniemulsion allows for the formation of nanometer-sized paramagnetic beads (~80 nm diameter), which were also evaluated as a contrast agent for MRI. These highly monodispersed, hybrid nanoparticles have enhanced properties, with the option for surface functionalization, making them a promising tool for biomedicine. Interestingly, both relaxivity measurements and MRI studies show that embedding the Mn8Fe4 core within a polymer matrix decreases r2 effects with little effect on r1, resulting in a positive T1 contrast enhancement.

[1]  Bo Zheng,et al.  Magnetic particle imaging (MPI) for NMR and MRI researchers. , 2013, Journal of magnetic resonance.

[2]  V. John,et al.  Superparamagnetic iron oxide nanoparticles with variable size and an iron oxidation state as prospective imaging agents. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[3]  S. Achilefu,et al.  Perspectives and potential applications of nanomedicine in breast and prostate cancer , 2013, Medicinal research reviews.

[4]  Antonio Garofalo,et al.  Manganese‐Enhanced MRI Contrast Agents: From Small Chelates to Nanosized Hybrids , 2012 .

[5]  Éva Tóth,et al.  Manganese(II) Complexes as Potential Contrast Agents for MRI , 2012 .

[6]  Samuel A Wickline,et al.  Manganese-based MRI contrast agents: past, present and future. , 2011, Tetrahedron.

[7]  M. Bau,et al.  Anthropogenic gadolinium as a microcontaminant in tap water used as drinking water in urban areas and megacities , 2011 .

[8]  Ralph Weissleder,et al.  Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy. , 2011, Accounts of chemical research.

[9]  William L. Boncher,et al.  Miniemulsion synthesis of metal-oxo cluster containing copolymer nanobeads. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[10]  N. Zhang,et al.  Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer. , 2011, Biomaterials.

[11]  G. Brudvig,et al.  Biocompatible and pH-sensitive PLGA encapsulated MnO nanocrystals for molecular and cellular MRI. , 2011, ACS nano.

[12]  M. Perazella,et al.  Imaging patients with kidney disease in the era of NSF: can it be done safely? , 2011, Clinical nephrology.

[13]  Lixin Wu,et al.  Mn12 single-molecule magnet aggregates as magnetic resonance imaging contrast agents. , 2011, Chemical communications.

[14]  Shelton D Caruthers,et al.  Revisiting an old friend: manganese-based MRI contrast agents. , 2011, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[15]  T. Meade,et al.  High-performance nanostructured MR contrast probes. , 2010, Nanoscale.

[16]  Jeffrey I. Zink,et al.  Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery , 2010, BiOS.

[17]  Katharina Landfester,et al.  From Polymeric Particles to Multifunctional Nanocapsules for Biomedical Applications Using the Miniemulsion Process , 2010 .

[18]  J. Weinreb,et al.  Gadolinium‐based contrast agents and nephrogenic systemic fibrosis: Why did it happen and what have we learned? , 2009, Journal of magnetic resonance imaging : JMRI.

[19]  Bejoy Thomas,et al.  Principles, techniques, and applications of T2*-based MR imaging and its special applications. , 2009, Radiographics : a review publication of the Radiological Society of North America, Inc.

[20]  S. Lofland,et al.  Surface attached manganese-oxo clusters as potential contrast agents. , 2009, Chemical communications.

[21]  Wenbin Lin,et al.  Manganese-based nanoscale metal-organic frameworks for magnetic resonance imaging. , 2008, Journal of the American Chemical Society.

[22]  J. Greneche,et al.  Coupling Agent Effect on Magnetic Properties of Functionalized Magnetite-Based Nanoparticles , 2008 .

[23]  C. Robic,et al.  Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. , 2008, Chemical reviews.

[24]  J. Cheon,et al.  Nanoscaling Laws of Magnetic Nanoparticles and Their Applicabilities in Biomedical Sciences , 2008 .

[25]  S. Nie,et al.  Reexamining the Effects of Particle Size and Surface Chemistry on the Magnetic Properties of Iron Oxide Nanocrystals: New Insights into Spin Disorder and Proton Relaxivity , 2008 .

[26]  X. Shuai,et al.  Folate-functionalized polymeric micelle as hepatic carcinoma-targeted, MRI-ultrasensitive delivery system of antitumor drugs , 2008, Biomedical microdevices.

[27]  Hang Sun,et al.  Incorporation of Polyoxometalates into Polystyrene Latex by Supramolecular Encapsulation and Miniemulsion Polymerization , 2008 .

[28]  Gang Bao,et al.  Coating thickness of magnetic iron oxide nanoparticles affects R2 relaxivity , 2007, Journal of magnetic resonance imaging : JMRI.

[29]  A. Durand,et al.  From polymeric surfactants to colloidal systems: 4. Neutral and anionic amphiphilic polysaccharides for miniemulsion stabilization and polymerization , 2007 .

[30]  S. Russek,et al.  The utility of the single-molecule magnet Fe8 as a magnetic resonance imaging contrast agent over a broad range of concentration , 2007 .

[31]  Oliver T. Bruns,et al.  Size and surface effects on the MRI relaxivity of manganese ferrite nanoparticle contrast agents. , 2007, Nano letters.

[32]  Sung Tae Kim,et al.  Development of a T1 contrast agent for magnetic resonance imaging using MnO nanoparticles. , 2007, Angewandte Chemie.

[33]  Xuxia Wang,et al.  Mn(II)-monosubstituted polyoxometalates as candidates for contrast agents in magnetic resonance imaging. , 2007, Journal of inorganic biochemistry.

[34]  Klaas Nicolay,et al.  MRI contrast agents: current status and future perspectives. , 2007, Anti-cancer agents in medicinal chemistry.

[35]  A. Djamali,et al.  Nephrogenic systemic fibrosis: risk factors and incidence estimation. , 2007, Radiology.

[36]  E. Kanal,et al.  Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. , 2007, Radiology.

[37]  C. Ladavière,et al.  Preparation of polysaccharide-coated nanoparticles by emulsion polymerization of styrene , 2007 .

[38]  T. Camesano,et al.  From polymeric surfactants to colloidal systems (2): Preparation of colloidal dispersions , 2006 .

[39]  Katharina Landfester,et al.  Synthesis and biomedical applications of functionalized fluorescent and magnetic dual reporter nanoparticles as obtained in the miniemulsion process , 2006 .

[40]  M. Port,et al.  Structural characterization of ultrasmall superparamagnetic iron oxide (USPIO) particles in aqueous suspension by energy dispersive X-ray diffraction (EDXD). , 2006, Journal of the American Chemical Society.

[41]  W. Koller,et al.  The diagnosis of manganese-induced parkinsonism. , 2006, Neurotoxicology.

[42]  J. VanMeter,et al.  Contrast-Enhanced In Vivo Imaging of Breast and Prostate Cancer Cells by MRI , 2006, Cell cycle.

[43]  A. Kent,et al.  Critical examination of Fe8 as a contrast agent for magnetic resonance imaging , 2005 .

[44]  C. Arús,et al.  In vitro characterization of an Fe8 cluster as potential MRI contrast agent , 2005, NMR in biomedicine.

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

[46]  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.

[47]  Alan P Koretsky,et al.  Sizing it up: Cellular MRI using micron‐sized iron oxide particles , 2005, Magnetic resonance in medicine.

[48]  Peter Caravan,et al.  Synthesis and evaluation of a high relaxivity manganese(II)-based MRI contrast agent. , 2004, Inorganic chemistry.

[49]  R. Clérac,et al.  Synthesis and characterization of magnetic organic-inorganic nanocomposites based on the [Mn2O12{CH2C(CH3)COO}16(H2O)4] building block , 2004 .

[50]  Alan P Koretsky,et al.  MRI detection of single particles for cellular imaging. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[51]  U. Schubert,et al.  Magnetic behaviour of a hybrid polymer obtained from ethyl acrylate and the magnetic cluster Mn12O12(acrylate)16 , 2004 .

[52]  S. Stoll Monolayer and Multilayer Films of [Mn12O12(O2CMe)16] , 2004 .

[53]  Z. J. Zhang,et al.  Effects of surface coordination chemistry on the magnetic properties of MnFe(2)O(4) spinel ferrite nanoparticles. , 2003, Journal of the American Chemical Society.

[54]  Q. Pankhurst,et al.  TOPICAL REVIEW: Applications of magnetic nanoparticles in biomedicine , 2003 .

[55]  M. Lowe MRI Contrast Agents: The Next Generation , 2002 .

[56]  W F Bennett,et al.  Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: Results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging , 2000, Journal of magnetic resonance imaging : JMRI.

[57]  E. Helmers,et al.  Hospital effluents as a source of gadolinium in the aquatic environment , 2000 .

[58]  R. Lauffer,et al.  Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. , 1999, Chemical reviews.

[59]  R. Bryant,et al.  Test of Electron Delocalization Effects on Water-Proton Spin-Lattice Relaxation by Bromination of [Tetrakis(4-sulfonatopheny)porphine]manganese. , 1999, Inorganic chemistry.

[60]  G. Christou,et al.  High-Spin Molecules: Iron(III) Incorporation into [Mn12O12(O2CMe)16(H2O)4] To Yield [Mn8Fe4O12(O2CMe)16(H2O)4] and Its Influence on the S = 10 Ground State of the Former , 1994 .

[61]  S M Wright,et al.  Liposome encapsulated MnCl2 as a liver specific contrast agent for magnetic resonance imaging. , 1990, Investigative radiology.

[62]  R. Balaban,et al.  Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo , 1989, Magnetic resonance in medicine.

[63]  L. Nordenskiöld,et al.  Theory of nuclear spin relaxation in paramagnetic systems in solution , 1986 .

[64]  P. Lauterbur,et al.  Image Formation by Induced Local Interactions: Examples Employing Nuclear Magnetic Resonance , 1973, Nature.

[65]  이재현 Chemical design of nanoparticle probes for high-performance magnetic resonance imaging , 2008 .

[66]  Jinwoo Cheon,et al.  Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging , 2007, Nature Medicine.

[67]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.

[68]  G. Elizondo,et al.  Preclinical evaluation of MnDPDP: new paramagnetic hepatobiliary contrast agent for MR imaging. , 1991, Radiology.

[69]  E. Roux,et al.  Contrast agents in magnetic resonance imaging. , 1988, Journal belge de radiologie.

[70]  Afonso C. Silva,et al.  Manganese‐enhanced magnetic resonance imaging (MEMRI) , 2004, NMR in biomedicine.