Sunghyun Kim

Aptide-conjugated liposome targeting tumor-associated fibronectin for glioma therapy

Aptides, developed by our laboratory, are a novel class of high-affinity peptides. Here, we describe the conjugation of an aptide targeting extra-domain B (EDB) of tumor-associated fibronectin to drug-containing liposomes and explore the potential of these aptide-conjugated liposomes as a robust and efficient targeted drug-delivery system for glioma therapy.

Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging.

Fibronectin extra domain B (EDB) is specifically expressed in cancer-associated blood vessels and extracellular matrix, and thus is a promising cancer biomarker. Very recently, we developed a novel class of high-affinity (<100nM) peptides, termed aptides, that specifically bind a variety of protein targets. Here, we describe superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with EDB-specific aptides for use in targeted magnetic resonance imaging (MRI) of cancer. An anti-EDB aptide (APT(EDB)) containing an additional cysteine residue reacted with maleimide-terminated, PEGylated phospholipid (Mal-PEG(2000)-DSPE) to give an aptide-conjugated PEGylated phospholipid (APT(EDB)-PEG(2000)-DSPE). A nanoemulsion method was then used to coat oleic acid-stabilized SPIONs with amphiphilic phospholipids, including APT(EDB)-PEG(2000)-DSPE, methoxy-PEG(2000)-DSPE, and rhodamine-DMPE. The resulting nanoparticles (APT(EDB)-SPIONs) had a hydrodynamic size of less than 50 nm and remained stable in an aqueous solution for at least 1week. In in vitro studies, APT(EDB)-SPIONs showed specific uptake by EDB-overexpressing cell lines. In an in vivo Lewis lung carcinoma model that expresses a high level of the target EDB protein, MRI clearly revealed that APT(EDB)-SPIONs injected via the tail vein specifically accumulated at the tumor site. Non-targeting SPIONs lacking the anti-EDB aptide showed much lower uptake in tumor tissues than did aptide-conjugated nanoparticles. Further, we confirmed that the distribution of nanoparticles within the tumor tissue was well correlated with the areas where EDB was expressed. Our APT(EDB)-SPIONs hold high potential as a specific imaging modality for the detection of EDB-overexpressing tumors.

A Specific STAT3-Binding Peptide Exerts Antiproliferative Effects and Antitumor Activity by Inhibiting STAT3 Phosphorylation and Signaling

STAT3 promotes the survival, proliferation, metastasis, immune escape, and drug resistance of cancer cells, making its targeting an appealing prospect. However, although multiple inhibitors of STAT3 and its regulatory or effector pathway elements have been developed, bioactive agents have been somewhat elusive. In this report, we report the identification of a specific STAT3-binding peptide (APTSTAT3) through phage display of a novel aptide library. APTSTAT3 bound STAT3 with high specificity and affinity (∼231 nmol/L). Addition of a cell-penetrating motif to the peptide to yield APTSTAT3-9R enabled uptake by murine B16F1 melanoma cells. Treatment of various types of cancer cells with APTSTAT3-9R blocked STAT3 phosphorylation and reduced expression of STAT targets, including cyclin D1, Bcl-xL, and survivin. As a result, APTSTAT3-9R suppressed the viability and proliferation of cancer cells. Furthermore, intratumoral injection of APTSTAT3-9R exerted potent antitumor activity in both xenograft and allograft tumor models. Our results offer a preclinical proof-of-concept for APTSTAT3 as a tractable agent for translation to target the broad array of cancers harboring constitutively activated STAT3.

Dipole-allowed direct band gap silicon superlattices.

Silicon is the most popular material used in electronic devices. However, its poor optical properties owing to its indirect band gap nature limit its usage in optoelectronic devices. Here we present the discovery of super-stable pure-silicon superlattice structures that can serve as promising materials for solar cell applications and can lead to the realization of pure Si-based optoelectronic devices. The structures are almost identical to that of bulk Si except that defective layers are intercalated in the diamond lattice. The superlattices exhibit dipole-allowed direct band gaps as well as indirect band gaps, providing ideal conditions for the investigation of a direct-to-indirect band gap transition. The fact that almost all structural portions of the superlattices originate from bulk Si warrants their stability and good lattice matching with bulk Si. Through first-principles molecular dynamics simulations, we confirmed their thermal stability and propose a possible method to synthesize the defective layer through wafer bonding.

Ab initio materials design using conformational space annealing and its application to searching for direct band gap silicon crystals

Abstract Lately, the so-called inverse method of materials design has drawn much attention, where specific material properties are initially assigned and target materials are subsequently searched for. Although this method has been successful for some problems, the success of designing complex crystal structures containing many atoms is often limited by the efficiency of the search method utilized. Here we combine the global optimization method of conformational space annealing (CSA) with first-principles quantum calculations and report a new scheme named AMADEUS ( Ab initio MAterials DEsign Using cSa). We demonstrate the utility of AMADEUS through the discovery of direct band gap Si crystals. The newly-designed direct gap Si allotropes show excellent optical properties and the spectroscopic limited maximum efficiencies comparable to those of best-known non-silicon photovoltaic materials. Our scheme not only provides a new perspective for the inverse problem of materials design but also may serve as a new tool for the computational design of a wide range of materials.

Stability and segregation of B and P dopants in Si/SiO2 core-shell nanowires.

Using molecular dynamics simulations, we generate realistic atomic models for oxidized Si nanowires which consist of a crystalline Si core and an amorphous SiO(2) shell. The amorphous characteristics of SiO(2) are well reproduced, as compared to those for bulk amorphous silica. Based on first-principles density functional calculations, we investigate the stability and segregation of B and P dopants near the radial interface between Si and SiO(2). Although substitutional B atoms are more stable in the core than in the oxide, B dopants can segregate to the oxide with the aid of Si self-interstitials which are generated during thermal oxidation. The segregation of B dopants occurs in the form of B interstitials in the oxide, leaving the self-interstitials in the Si core. In the case of P dopants, dopant segregation to the oxide is unfavorable even in the presence of self-interstitials. Instead, we find that P dopants tend to aggregate in the Si region near the interface and may form nearest-neighbor donor pairs, which are energetically more stable than isolated P dopants.

Selective discrete wavelet packet trnasform-based energy detector for cognitive radios

Spectrum sensing, a technique to recognize unused or idle spectrum, is a key function for cognitive radio (CR) and requires high precision and fast signal processing technique. To satisfy these requirements, two-stage sensing architecture that combines an energy detector and a feature detector was proposed by IEEE 802.22 working group (WG). For an energy detector, various techniques such as receive signal strength indicator (RSSI), multi resolution spectrum sensing (MRSS), fast Fourier transform (FFT) have been suggested and recently discrete wavelet packet transform (DWPT)-based method was proposed. In this paper, we propose a modified DWPT-based energy detector by using half-band elliptic IIR filters and double threshold method. Through simulation and complexity analysis, it is shown that the proposed scheme can reduce computational complexity and false detection probability compared to conventional DWPT-based energy detector for spectrum sensing in CR.

Comparison of conductive fabric sensor and Ag-AgCl sensor under motion artifacts

A wearable electrocardiogram(ECG) device using conductive fabric sensor was compared with traditional Ag-AgCl electrode ECG device. The ECG signals were measured under existence of motion artifacts on variable running speed using treadmill to verify that wearable device can substitute traditional ECG device. A signal to noise ratio (SNR) and RR interval were compared between the two devices. The SNR of wearable device was similar or higher than that of clinical device and difference of RR interval was 2ms. The results show that the wearable ECG device using conductive fabric sensor can make similar performance with ECG device using Ag-AgCl electrode even under motion artifacts.

Synthesis and Characterization of Novel Amine-Contained Electroluminescent Polymer

Abstract A new type of processable electroluminescent polymer containing tertiary amine linkage was prepared by typical Wittig reaction between bis(4-formylphenyl) n-butylamine and diphosphonium salt. The resulting polymer was highly soluble in common organic solvents so that it could be spun-cast onto glass plate coated with ITO electrode to give highly transparent homogeneous thin film. The molecular weight of the polymer determined by gel permeation chromatography using polystyrene standards is Mn = 4,500, Mw = 11,600. The structure of the polymer was confirmed by IR, UV-visible, and 1H-and 13C-NMR spectroscopy. We observed successfully the electroluminescence peaked at around 530 nm from the device made of the synthesized polymer. The current-voltage (I-V) curves showed typical rectifying diode characteristic.

Prediction of Green Phosphorus with Tunable Direct Band Gap and High Mobility

Black phosphorus is an emerging material in nanoelectronics and nanophotonics due to its high carrier mobility and anisotropic in-plane properties. In addition, the polymorphism of phosphorus leads to numerous searches for new allotropes that are more attractive than black phosphorus in a variety of applications. On the basis of ab initio evolutionary crystal structure search computation, we report the prediction of a phosphorus allotrope called green phosphorus (λ-P), which exhibits direct band gaps ranging from 0.7 to 2.4 eV and strong anisotropy in optical and transport properties. Free-energy calculations show that a single-layer form, termed green phosphorene, is energetically more stable than blue phosphorene, and a phase transition from black to green phosphorene can occur at temperatures above 87 K. We suggest that green phosphorene can be synthesized on corrugated metal surfaces rather than clean surfaces due to its buckled structure, providing guidance to achieving epitaxial growth.Based on ab initio evolutionary crystal structure search computation, we report a new phase of phosphorus called green phosphorus (λ-P), which exhibits the direct band gaps ranging from 0.7 to 2.4 eV and the strong anisotropy in optical and transport properties. Free energy calculations show that a single-layer form, termed green phosphorene, is energetically more stable than blue phosphorene and a phase transition from black to green phosphorene can occur at temperatures above 87 K. Due to its buckled structure, green phosphorene can be synthesized on corrugated metal surfaces rather than clean surfaces.