Kyoung-Ran Kim

Sentinel lymph node imaging by a fluorescently labeled DNA tetrahedron.

Sentinel lymph nodes (SLNs) are the first lymph nodes which cancer cells reach after traveling through lymphatic vessels from the primary tumor. Evaluating the nodal status is crucial in accurate staging of human cancers and accordingly determines prognosis and the most appropriate treatment. The commonly used methods for SLN identification in clinics are based on employment of a colloid of radionuclide or injection of a small dye. Although these methods have certainly contributed to improve surgical practice, new imaging materials are still required to overcome drawbacks of the techniques such as inconvenience of handling radioactive materials and short retention time of small dyes in SLNs. Here, we prepare a fluorescence-labeled DNA tetrahedron and perform SLN imaging by using the DNA nanoconstruct. With a successful identification of SLNs by the DNA nanoconstruct, we suggest that DNA tetrahedron hold great promises for clinical applications.

Reversible Regulation of Enzyme Activity by pH-Responsive Encapsulation in DNA Nanocages

Reversible regulation of enzyme activity by chemical and physical stimuli is often achieved by incorporating stimuli-responsive domains in the enzyme of interest. However, this method is suitable for a limited number of enzymes with well-defined structural and conformational changes. In this study, we present a method to encapsulate enzymes in a DNA cage that could transform its conformation depending on the pH, allowing reversible control of the accessibility of the enzyme to the surrounding environment. This enabled us to regulate various properties of the enzyme, such as its resistance to protease-dependent degradation, binding affinity to the corresponding antibody, and most importantly, enzyme activity. Considering that the size and pH responsiveness of the DNA cage can be easily adjusted by the DNA length and sequence, our method provides a broad-impact platform for controlling enzyme functions without modifying the enzyme of interest.

Modulating α-synuclein fibril formation using DNA tetrahedron nanostructures

The small presynaptic protein α-synuclein (α-syn) is involved in the etiology of Parkinsons disease owing to its abnormal misfolding. To date, little information is known on the role of DNA nanostructures in the formation of α-syn amyloid fibrils. Here, the effects of DNA tetrahedrons on the formation of α-syn amyloid fibrils were investigated using various biochemical and biophysical methods such as thioflavin T fluorescence assay, atomic force microscopy, light scattering, transmission electron microscopy, and cell-based cytotoxicity assay. It has been shown that DNA tetrahedrons decreased the level of oligomers and increased the level of amyloid fibrils, which corresponded to decreased cellular toxicity. The ability of DNA tetrahedron to facilitate the formation of α-syn amyloid fibrils demonstrated that structured nucleic acids such as DNA tetrahedrons could modulate the process of amyloid fibril formation. Our study suggests that DNA tetrahedrons could be used as an important facilitator toward amyloid fibril formation of α-synuclein, which may be of significance in finding therapeutic approaches to Parkinsons disease and related synucleinopathies.

Shaping Rolling Circle Amplification Products into DNA Nanoparticles by Incorporation of Modified Nucleotides and Their Application to In Vitro and In Vivo Delivery of a Photosensitizer

Rolling circle amplification (RCA) is a robust way to generate DNA constructs, which are promising materials for biomedical applications including drug delivery because of their high biocompatibility. To be employed as a drug delivery platform, however, the DNA materials produced by RCA need to be shaped into nanoparticles that display both high cellular uptake efficiency and nuclease resistance. Here, we showed that the DNA nanoparticles (DNPs) can be prepared with RCA and modified nucleotides that have side-chains appended on the nucleobase are capable of interacting with the DNA strands of the resulting RCA products. The incorporation of the modified nucleotides improved cellular uptake efficiency and nuclease resistance of the DNPs. We also demonstrated that these DNPs could be employed as carriers for the delivery of a photosensitizer into cancer cells to achieve photodynamic therapy upon irradiation at both the in vitro and in vivo levels.

SOA/BPM‐based Dynamic SW Integration Scheme for Various Bioinformatics Tools

As numerous software tools have been developed in the bioinformatics, flexible integration or modification of conventional tools is an important issue. Many researchers want to combine these tools for their purpose both in vivo and in silico. Recently, SOA (service‐oriented architecture) and BPM (business process management) are emerging as an ultimate solution for efficient and flexible software integration or modification. They provide loosely coupled integration instead of previous tightly coupled integration approaches. In the loosely coupled integration, component systems can be modified or replaced freely and some components in a system may reside in remote systems in the web service style. In this paper, we present an SOA/BPM‐based integration scheme for various software tools in bioinformatics. We apply the scheme in the EST analysis, which consists of multiple components and steps, and verify the usefulness of the integration scheme.

Necrosis of Carcinoma Cells Using

The purpose of this study was to investigate the cell necrosis by the hysteric heating of Co/sub 1-x/Ni/sub x/Fe/sub 2/O/sub 4/ and Ba/sub 1-x/Sr/sub x/Fe/sub 12/O/sub 19/ ferrites under external magnetic field with respect to applications in hyperthermic cancer treatments. Co/sub 1-x/Ni/sub x/Fe/sub 2/O/sub 4/ and Ba/sub 1-x/Sr/sub x/Fe/sub 12/O/sub 19/ ferrites were synthesized by a sol-gel process. Variation of the temperature as a result of hysteresis heating was measured as a function of the exposure time to the external alternating magnetic field at frequencies of 0.1 /spl sim/ 15 MHz. A human squamous cell carcinoma KB cell line was selected to determine the effect of the synthesized ferrites on the destruction of carcinoma cells in vitro using a methylthiazol tetrazolium bromide (MTT) method. When a CoFe/sub 2/O/sub 4/ disc was placed in 0.2 ml of distilled water, the greatest temperature change (/spl Delta/T=29.3/spl deg/C) was observed. More than half of the malignant carcinoma cells were dead after being exposed to the 7-MHz ac magnetic field for 1 h by CoFe/sub 2/O/sub 4/ ferrites, while normal cells survived more than 60% of the time.