Byung Hyo Kim

Large-Scale Synthesis of Uniform and Extremely Small-Sized Iron Oxide Nanoparticles for High-Resolution T1 Magnetic Resonance Imaging Contrast Agents

Uniform and extremely small-sized iron oxide nanoparticles (ESIONs) of < 4 nm were synthesized via the thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. Oleyl alcohol lowered the reaction temperature by reducing iron-oleate complex, resulting in the production of small-sized nanoparticles. XRD pattern of 3 nm-sized nanoparticles revealed maghemite crystal structure. These nanoparticles exhibited very low magnetization derived from the spin-canting effect. The hydrophobic nanoparticles can be easily transformed to water-dispersible and biocompatible nanoparticles by capping with the poly(ethylene glycol)-derivatized phosphine oxide (PO-PEG) ligands. Toxic response was not observed with Fe concentration up to 100 μg/mL in MTT cell proliferation assay of POPEG-capped 3 nm-sized iron oxide nanoparticles. The 3 nm-sized nanoparticles exhibited a high r(1) relaxivity of 4.78 mM(-1) s(-1) and low r(2)/r(1) ratio of 6.12, demonstrating that ESIONs can be efficient T(1) contrast agents. The high r(1) relaxivities of ESIONs can be attributed to the large number of surface Fe(3+) ions with 5 unpaired valence electrons. In the in vivo T(1)-weighted magnetic resonance imaging (MRI), ESIONs showed longer circulation time than the clinically used gadolinium complex-based contrast agent, enabling high-resolution imaging. High-resolution blood pool MR imaging using ESIONs enabled clear observation of various blood vessels with sizes down to 0.2 mm. These results demonstrate the potential of ESIONs as T(1) MRI contrast agents in clinical settings.

Galvanic Replacement Reactions in Metal Oxide Nanocrystals

Hollowing Out Metal Oxide Nanoparticles Corrosion is normally a problem, but it can be useful, for example, when you wish to create hollow metal nanoparticles, whereby the reduction of one metal species in solution drives the dissolution of the core of the particle. Oh et al. (p. 964; see the Perspective by Ibáñez and Cabot) adapted this approach to metal oxide nanoparticles by placing Mn3O4 nanocrystals in solution with Fe2+ ions, which replaces the nanocrystal exterior with γ-Fe2O3. At sufficiently high Fe2+ concentrations, hollow γ-Fe2O3 nanocages formed. These hollow structures could be used as anode materials for lithium ion batteries. Hollow mixed-metal oxide nanoparticles can be made by replacing the metal cations through redox reactions in solution. [Also see Perspective by Ibáñez and Cabot] Galvanic replacement reactions provide a simple and versatile route for producing hollow nanostructures with controllable pore structures and compositions. However, these reactions have previously been limited to the chemical transformation of metallic nanostructures. We demonstrated galvanic replacement reactions in metal oxide nanocrystals as well. When manganese oxide (Mn3O4) nanocrystals were reacted with iron(II) perchlorate, hollow box-shaped nanocrystals of Mn3O4/γ-Fe2O3 (“nanoboxes”) were produced. These nanoboxes ultimately transformed into hollow cagelike nanocrystals of γ-Fe2O3 (“nanocages”). Because of their nonequilibrium compositions and hollow structures, these nanoboxes and nanocages exhibited good performance as anode materials for lithium ion batteries. The generality of this approach was demonstrated with other metal pairs, including Co3O4/SnO2 and Mn3O4/SnO2.

Synthesis of Uniform Ferrimagnetic Magnetite Nanocubes

We synthesized uniform ferrimagnetic magnetite nanocubes in the size range from 20 to 160 nm. The magnetic property of the nanocubes was characterized, and magnetic separation of the histidine-tagged protein was demonstrated.

Multifunctional Fe3O4/TaOx Core/Shell Nanoparticles for Simultaneous Magnetic Resonance Imaging and X-ray Computed Tomography

Multimodal imaging is highly desirable for accurate diagnosis because it can provide complementary information from each imaging modality. In this study, a sol-gel reaction of tantalum(V) ethoxide in a microemulsion containing Fe(3)O(4) nanoparticles (NPs) was used to synthesize multifunctional Fe(3)O(4)/TaO(x) core/shell NPs, which were biocompatible and exhibited a prolonged circulation time. When the NPs were intravenously injected, the tumor-associated vessel was observed using computed tomography (CT), and magnetic resonance imaging (MRI) revealed the high and low vascular regions of the tumor.

Magnetosome-like ferrimagnetic iron oxide nanocubes for highly sensitive MRI of single cells and transplanted pancreatic islets

For ultrasensitive magnetic resonance imaging (MRI), magnetic nanoparticles with extremely high r2 relaxivity are strongly desired. Magnetosome-like nanoparticles were prepared by coating polyethylene glycol-phospholipid (PEG-phospholipid) onto ferrimagnetic iron oxide nanocubes (FIONs). FIONs exhibited a very high relaxivity (r2) of 324 mM-1 s-1, allowing efficient labeling of various kinds of cells. The magnetic resonance (MR) imaging of single cells labeled with FIONs is demonstrated not only in vitro but also in vivo. Pancreatic islet grafts and their rejection could be imaged using FIONs on a 1.5 T clinical MRI scanner. The strong contrast effect of FIONs enabled MR imaging of transplanted islets in small rodents as well as in large animals. Therefore, we expect that MR imaging of pancreatic islet grafts using FIONs has the potentials for clinical applications. Furthermore, FIONs will enable highly sensitive noninvasive assessment after cell transplantation.

Enhancement of neurite outgrowth in PC12 cells by iron oxide nanoparticles

Despite the many potential therapeutic applications of iron oxide nanoparticle such as its use as an imaging and targeting tool, its biological effects have not yet been extensively characterized. Herein, we report that iron oxide nanoparticles taken up by PC12 cells can enhance neurite outgrowth. PC12 cells exposed to both iron oxide nanoparticles and nerve growth factor (NGF) synergistically increased the efficiency of neurite outgrowth in a dose-dependent manner. This may have resulted from the activation of cell adhesion molecules that are associated with cell-matrix interactions through iron. Immunoblotting assays also revealed that both neural specific marker protein and cell adhesion protein expression were upregulated by iron oxide nanoparticles compared with non-treated cells via activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Our findings point to the possibility that iron oxide nanoparticles can affect cell-substrate interactions and regulate cell behaviors, which provides clinical insights into potential neurologic and therapeutic applications of iron oxide nanoparticles.

Multifunctional mesoporous silica nanocomposite nanoparticles for pH controlled drug release and dual modal imaging

Multifunctional nanocomposite nanoparticles for simultaneous fluorescence and magnetic resonance (MR) imaging, and pH-sensitive drug release were fabricated by immobilizing pH responsive hydrazone bonds, magnetite nanoparticles and fluorescent dyes in mesoporous silica nanoparticles. pH dependent release of doxorubicin was demonstrated and the nanocomposite nanoparticles show fluorescence emission and MR contrast effect.

Paramagnetic inorganic nanoparticles as T1 MRI contrast agents

Magnetic resonance imaging (MRI) is one of the most powerful molecular imaging techniques and can noninvasively visualize and quantify biological processes within the living organisms. The introduction of exogenous contrast agents has allowed specific visualization of biological targets as well as enhanced the sensitivity of MRI. Recently, paramagnetic inorganic nanoparticles showing positive T(1) contrast effect have been investigated as T(1) MRI contrast agents. Since the first trials of spherical nanoparticles of manganese oxide and gadolinium oxide, inorganic nanoparticles of various compositions and shapes have been used for in vivo and in vitro MRI because of their distinct signal enhancement in MR images. However, for clinical applications, important and complex issues such as safety and efficiency should be investigated by active research encompassing multiple disciplines, including chemistry, biology, biomedical engineering, and medicine.

Transformation of hydrophobic iron oxide nanoparticles to hydrophilic and biocompatible maghemite nanocrystals for use as highly efficient MRI contrast agent

We report a transformation of hydrophobic iron oxide nanoparticles to hydrophilic and biocompatible maghemite nanocrystals by controlled thermal treatment followed by dextran coating. Sodium sulfate salt was used as matrix for preventing aggregation during the thermal treatment at high temperature. Through the thermal treatment and subsequent isolation process, highly crystalline bare maghemite nanocrystals with high magnetization were produced. Subsequent coating with dextran derivatives produced hydrophilic and biocompatible iron oxide nanocrystals. Among various kinds of dextran derivatives, polyanionic carboxymethyl dextran (CM-dextran) was most efficient for stabilizing the nanocrystals in aqueous media. CM-dextran coated nanocrystals exhibited high relaxivity originating from the high magnetization and assembled structure.

Sizing by Weighing: Characterizing Sizes of Ultrasmall-Sized Iron Oxide Nanocrystals Using MALDI-TOF Mass Spectrometry

We present a rapid and reliable method for determining the sizes and size distributions of <5 nm-sized iron oxide nanocrystals (NCs) using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS). MS data were readily converted to size information using a simple equation. The size distribution obtained from the mass spectrum is well-matched with the data from transmission electron microscopy, which requires long and tedious analysis work. The size distribution obtained from the mass spectrum is highly resolved and can detect size differences of only a few angstroms. We used this MS-based technique to investigate the formation of iron oxide NCs, which is not easy to monitor with other methods. From ex situ measurements, we observed the transition from molecular precursors to clusters and then finally to NCs.