Yuna Choi

A highly crystalline manganese-doped iron oxide nanocontainer with predesigned void volume and shape for theranostic applications

Hollow Mn-doped iron oxide nanocontainers, formed by a novel one-pot synthetic process, fulfill the dual requirements of delivering an effective dose of an anticancer drug to tumor tissue and enabling image-contrast monitoring of the nanocontainer fate through T2 -weighted magnetic resonance imaging, thereby determining the optimal balance between diagnostic and therapeutic moieties in an all-in-one theranostic nanoplatform.

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.

Terahertz spectroscopic imaging and properties of gastrointestinal tract in a rat model

We have investigated basic properties of normal gastrointestinal (GI) tract tissues, including glandular stomach (GS), fore stomach (FS), large intestine (LI), small intestine (SI), and esophagus (ESO), from a rat model using terahertz (THz) reflection imaging and spectroscopy. The THz images collected from stratified squamous epithelia (SSE) of FS and ESO show a lower peak-to-peak value compared to those from columnar epithelia (CE) of GS, LI, or SI because the SSE contains less water than CE. The refractive index and absorption coefficient of FS were less than those of GS or LI, both having values similar to those of water. Additionally, we report internal reflection THz signals from ESO, although we were unable to determine the exact interface for this internal reflection.

π-Hyaluronan nanocarriers for CD44-targeted and pH-boosted aromatic drug delivery

Molecular targeted delivery of therapeutic agents and their stimuli-responsive release are some of the major issues for modern medical administration, particularly in cancer chemotherapy. In this study, we developed a π-hyaluronan nanocarrier (πHNC) for CD44-targeted and pH-boosted delivery of an aromatic anticancer drug to cancer cells. Amphiphilic π-hyaluronan (pyrenyl hyaluronan, πHA) was synthesized using EDC chemistry, and self-assembled to form πHNC, the structure of which was obviously micellar but was convincingly effective to function; (i) a π-rich pyrenyl core of πHNC, a loading aromatic drug (doxorubicin, DOX) by π-stacking attraction, showed a rapid release profile under low pH conditions which is a notable characteristic of the cancer microenvironment as well as the endolysosomal state after uptake into the target cell and (ii) the hydrophilic hyaluronan shell of πHNC acted as a ligand for CD44 resulting in the localization of πHNC into the target cell by CD44-mediated endocytosis, without cytotoxicity. With its targeted and stimulated delivery of aromatic drugs to the target cells, DOX-loaded πHNC (πHNC/DOX) provided effectual therapeutic activity in both in vitro and in vivo models of CD44-positive human gastric cancer, which is suitable as a facile and efficient drug delivery platform.

Terahertz reflectometry imaging for low and high grade gliomas

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

Population-specific spectrum of the F11 mutations in Koreans: evidence for a founder effect.

Kim J, Song J, Lyu CJ, Kim YR, Oh SH, Choi YC, Yoo JH, Choi JR, Kim H, Lee K‐A. Population‐specific spectrum of the F11 mutations in Koreans: evidence for a founder effect.

An aggressive form of familial amyloid polyneuropathy caused by a Glu54Gly mutation in the transthyretin gene

We report a patient with familial amyloid polyneuropathy. Gene analysis revealed a heterozygous Glu54Gly substitution (A‐to‐G change) in the transthyretin gene. This is the first case of a Glu54Gly substitution that was devoid of a Gly6Ser substitution. Compared with the previously reported case with compound heterozygotes of Glu54Gly and Gly6Ser, the age of onset in our case is much younger and another characteristic findings were the amyloid vasculopathy and the multiple organ involvement. A Glu54Gly mutation is amyloidogenic by itself and a Gly6Ser mutation may offer some protection from the Glu54Gly mutant.

Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

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.

Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders

Inherited muscular disorders (IMDs) are clinically and genetically heterogeneous genetic disorders. We investigated the mutational spectrum and genotype–phenotype correlations in Korean patients with IMD. We developed a targeted panel of 69 known IMD genes and recruited a total of 209 Korean patients with IMD. Targeted capture sequencing identified 994 different variants. Among them, 98 variants were classified as pathogenic/likely pathogenic variants; 38 were novel variations. A total of 39 patients had the pathogenic/likely pathogenic variants. Among them, 75 (36%) patients were genetically confirmed, and 18 (9%) patients had one heterozygous variant of recessive myopathy. However, two genetically confirmed patients had an additional heterozygous variant of another recessive myopathy. Four patients with one heterozygous variant of a recessive myopathy showed different phenotypes, compared with the known phenotype of the identified gene. The major causative genes of Korean patients with IMDs were DMD (19 patients), COL6A1 (9), DYSF (9), GNE (7), LMNA (7), CAPN3 (6), and RYR1 (5). This study showed the mutational and clinical spectra in Korean patients with IMD and confirmed the usefulness of strategies utilizing targeted sequencing.