Bongjune Kim

Dextran-coated magnetic nanoclusters as highly sensitive contrast agents for magnetic resonance imaging of inflammatory macrophages

We fabricated dextran-coated magnetic nanoclusters (Dex-MNCs) for targeted magnetic resonance (MR) imaging of inflammatory macrophages. Dex-MNCs were prepared through encapsulation of hydrophobic magnetic nanocrystals (MNCs) by pyrenyl dextran in order that MNCs could achieve increased colloidal stability in aqueous phase as well as strongly interact with macrophages. Dex-MNCs exhibited biocompatibility and sufficient targeting efficiency against macrophages with strengthened MR contrast effect from in vitro/in vivo studies. Considering these results, we confirmed that Dex-MNCs could accurately detect inflammatory macrophagevia MR imaging.

Aptamer‐conjugated magnetic nanoparticles enable efficient targeted detection of integrin αvβ3 via magnetic resonance imaging

An understanding of neovascularization and/or angiogenesis in cancer is acutely required for effective cancer therapy due to concerns about tumor growth and metastasis. In particular, integrin αvβ3 is closely associated with cell migration and invasion during angiogenesis. Hence, we developed aptamer(αvβ3)-conjugated magnetic nanoparticles (Apt(αvβ3)-MNPs) to enable precise detection of integrin-expressing cancer cells using magnetic resonance imaging. Apt(αvβ3)-MNPs exhibited not only cytocompatibility, but also an efficient targeting ability with high magnetic sensitivity through in vitro/in vivo studies. The results of this study demonstrate that Apt(αvβ3)-MNPs have the potential to be used for accurate tumor diagnosis and therapy.

Aptamer-modified magnetic nanoprobe for molecular MR imaging of VEGFR2 on angiogenic vasculature

Nucleic acid-based aptamers have been developed for the specific delivery of diagnostic nanoprobes. Here, we introduce a new class of smart imaging nanoprobe, which is based on hybridization of a magnetic nanocrystal with a specific aptamer for specific detection of the angiogenic vasculature of glioblastoma via magnetic resonance (MR) imaging. The magnetic nanocrystal imaging core was synthesized using the thermal decomposition method and enveloped by carboxyl polysorbate 80 for water solubilization and conjugation of the targeting moiety. Subsequently, the surface of the carboxylated magnetic nanocrystal was modified with amine-functionalized aptamers that specifically bind to the vascular growth factor receptor 2 (VEGFR2) that is overexpressed on angiogenic vessels. To assess the targeted imaging potential of the aptamer-conjugated magnetic nanocrystal for VEGFR2 markers, the magnetic properties and MR imaging sensitivity were investigated using the orthotopic glioblastoma mouse model. In in vivo tests, the aptamer-conjugated magnetic nanocrystal effectively targeted VEGFR2 and demonstrated excellent MR imaging sensitivity with no cytotoxicity.

Continuous coaxial electrohydrodynamic atomization system for water-stable wrapping of magnetic nanoparticles.

An electrohydrodynamic atomization (EHDA) system that generates an electrospray can achieve particle formation and encapsulation by accumulating an electric charge on liquid flowing out from the nozzle. A novel coaxial EHDA system for continuous fabrication of water-stable magnetic nanoparticles (MNPs) is established, based on a cone-jet mode of electrospraying. Systemic variables, such as flow rates from dual nozzles and inducing voltages, are controlled to enable the preparation of water-soluble MNPs coated by polysorbate 80. The PEGylated MNPs exhibit water stability. The magnetic resonance imaging potential of these MNPs is confirmed by in vivo imaging using a gastric cancer xenograft mouse model. Thus, this advanced coaxial EHDA system demonstrates remarkable capabilities for the continuous encapsulation of MNPs to render them water-stable while preserving their properties as imaging agents.

Magnetic Nanoclusters Engineered by Polymer-Controlled Self-Assembly for the Accurate Diagnosis of Atherosclerotic Plaques via Magnetic Resonance Imaging†

Oleyl dextran-coated magnetic nanoclusters (ODMCs) are fabricated for the accurate detection of macrophage-rich atherosclerotic plaques using magnetic resonance (MR) imaging. Dextran is introduced to the cluster surface of magnetic nanocrystals (MNCs) through self-assembly using amphiphilic oleic acid-conjugated dextran (ODex) to provide not only hydrophilicity but also a high affinity to macrophages. Enhanced magnetism of the ODMCs is engineered by optimizing the degree of substitution (DS) of the oleyl group in ODex and the concentration of ODex used for the synthesis of ODMC. Consequently, ODMCs exhibit significantly increased T2 relaxivity and excellent macrophage-targeting ability without cytotoxicity, in vitro. Moreover, in vivo T2-weighted MR imaging after intravenous injection of ODMCs into a rat artery balloon injury model demonstrates considerable MR contrast strength efficacy in the plaques of the injured carotid artery. These novel ODMCs may offer a highly efficient MR imaging nanoprobes for the selective diagnosis of atherosclerosis.

Double-ligand modulation for engineering magnetic nanoclusters

Magnetic nanoclusters (MNCs) are agglomerated individual magnetic nanoparticles (MNPs) that show great promise in increasing magnetic resonance imaging (MRI) sensitivity. Here, we report an effective strategy to engineer MNCs based on double-ligand modulation to enhance MRI sensitivity. The oleic acid-coated individual MNPs self-assembled and then were enveloped by polysorbate 80, using a nanoemulsion method to prepare MNCs. By modulating the amounts of the two ligands, and thus the size and magnetic content of the resultant MNCs, we were able to enormously improve MRI sensitivity.

Maleimidyl magnetic nanoplatform for facile molecular MRI

In this study, we developed the maleimidyl magnetic nanoplatform, which enables functional targeting of a biomarker-specific moiety for molecular imaging via MRI. The maleimide group of the maleimidyl magnetic nanoplatform is conjugated with a thiol group without additional crosslinkers and side products. A physicochemical analysis was conducted to verify the effectiveness of the maleimidyl magnetic nanoplatform, and the existence of the maleimidyl group was investigated using the platform. To prepare biomarker-specific MRI probes, a thiolated aptamer and peptide were immobilized onto the maleimidyl group of the maleimidyl magnetic nanoplatform. The fabricated MRI probes were applied to four cancer cell lines: HT1080, MCF7, MKN45, and HEK293T. To investigate the potential of the molecular MRI probe, the target-biomarker specificity was confirmed without serious cytotoxicity, and in vivo MRI analysis using a xenograft mouse model was demonstrated. We believe these results will be useful for fabricating molecular MRI probes for the diagnosis of cancer.

T 2 - and T*2-weighted MRI of rat glioma using polysorbate-coated magnetic nanocrystals as a blood-pool contrast agent

In this study, T2- and T*2-weighted imaging potential of polysorbate-coated magnetic nanocrystals (P-MNCs) was investigated as a blood-pool contrast agent using a 9L-rat glioma model after intravenous injection via 3.0T MRI. Magnetic nanocrystals (MNCs, Fe3O4) synthesized by the thermal decomposition method were coated with polysorbate 80 using a nanoemulsion method to generate a water-stable MRI contrast agent. The physical properties and MR imaging capability of P-MNCs were verified. The orthotopic tumor models were established by implanting 9L-rat glioma cells into the rat brain. After tail-vein injection of P-MNCs, T2- and T*2-weighted imaging of tumor sites was performed. Blood clearance and biodistribution studies were also performed. The hydrodynamic diameter of P-MNCs was 10.5 ± 0.8 nm and a spherical magnetic core was confirmed. The r2 value of P-MNCs was calculated to be 114.1 mM−1 s−1. Heterogeneous contrast T2-weighted MRI images of the 9L-rat glioma model were visualized at the tumor site before injecting the MRI contrast agent. In particular, T*2-weighted images demonstrated more obvious signal intensity changes than did T2-weighted images. Neovasculature in the tumor tissue was clearly observed in T*2 images compared with T2-weighted images. The blood half-life of P-MNCs was 2 h and the Fe ion concentration of blood had returned to the baseline after 16 h. Well-tailored P-MNCs can be effectively used as a novel MRI contrast agent for visualizing of vasculatures for solid tumors via T2- and T*2-weighted imaging.

Compensatory UTE/T2W Imaging of Inflammatory Vascular Wall in Hyperlipidemic Rabbits.

Objectives To obtain compensatory ultra-short echo time (UTE) imaging and T2-weighted (T2W) imaging of Watanabe heritable hyperlipidemic (WHHL) rabbits following dextran-coated magnetic nanocluster (DMNC) injection for the effective in vivo detection of inflammatory vascular wall. Methods Magnetic nanoparticle was synthesized by thermal decomposition and encapsulated with dextran to prepare DMNC. The contrast enhancement efficiency of DMNC was investigated using UTE (repetition time [TR] = 5.58 and TE = 0.07 ms) and T2W (TR = 4000 and TE = 60 ms) imaging sequences. To confirm the internalization of DMNC into macrophages, DMNC-treated macrophages were visualized by cellular transmission electron microscope (TEM) and magnetic resonance (MR) imaging. WHHL rabbits expressing macrophage-rich plaques were subjected to UTE and T2W imaging before and after intravenous DMNC (120 μmol Fe/kg) treatment. Ex vivo MR imaging of plaques and immunostaining studies were also performed. Results Positive and negative contrast enhancement of DMNC solutions with increasing Fe concentrations were observed in UTE and T2W imaging, respectively. The relative signal intensities of the DMNC solution containing 2.9 mM Fe were calculated as 3.53 and 0.99 in UTE and T2W imaging, respectively. DMNC uptake into the macrophage cytoplasm was visualized by electron microscopy. Cellular MR imaging of DMNC-treated macrophages revealed relative signals of 3.00 in UTE imaging and 0.98 in T2W imaging. In vivo MR images revealed significant brightening and darkening of plaque areas in the WHHL rabbit 24 h after DMNC injection in UTE and T2W imaging, respectively. Ex vivo MR imaging results agreed with these in vivo MR imaging results. Histological analysis showed that DMNCs were localized to areas of inflammatory vascular wall. Conclusions Using compensatory UTE and T2W imaging in conjunction with DMNC is an effective approach for the noninvasive in vivo imaging of atherosclerotic plaque.

Iatrogenic Pseudoaneurysm of the Meningohypophyseal Trunk; A Rare Complication of Trans-sphenoidal Surgery

This 33-year-old man was diagnosed with pituitary macroadenoma and underwent microscopic trans-sphenoidal resection in the department of neurosurgery. His laboratory finding showed an increased level of prolactin and he had no neurologic deficit. Magnetic resonance imaging (MRI) showed a pituitary macroadenoma with invasion of the right cavernous sinus. Previously, he was not administered with bromocriptine. During exposure of the sella via a trans-sphenoidal access, it was found that the residual tumor was attached to the right cavernous sinus. In an attempt of tumor resection, it was complicated due to unexpected intraoperative arterial bleeding, which was temporarily arrested by nasal packing using gelfoam and hemostatic matrix (FloSeal; Baxter Inc., Deerfield, IL). The patient remained intact without neurologic deficit. Immediately after operation, brain MRI showed formation of a pseudoaneurysm near the resection margin, and cerebral angiography revealed a 2.5 mm-sized pseudoaneurysm from the right MHT (Fig. 1a and b). EVT was decided due to the patient’s condition and surgical risk, and an informed consent was obtained. Via the right femoral artery access, a 6 Fr guiding catheter (Envoy, Codman Neurovascular, Raynham, MA) was introduced into the right ICA. A 2.0 Fr microcatheter (preshaped J Excelsior, Stryker, Fremont, CA) was navigated into the proximal MHT under guidance of a 0.014-inch microwire (Synchro-2, Stryker) and advanced into the saccular lumen Introduction