H.-R. Kim

Observation of terahertz-radiation-induced ionization in a single nano island

Terahertz (THz) electromagnetic wave has been widely used as a spectroscopic probe to detect the collective vibrational mode in vast molecular systems and investigate dielectric properties of various materials. Recent technological advances in generating intense THz radiation and the emergence of THz plasmonics operating with nanoscale structures have opened up new pathways toward THz applications. Here, we present a new opportunity in engineering the state of matter at the atomic scale using THz wave and a metallic nanostructure. We show that a medium strength THz radiation of 22 kV/cm can induce ionization of ambient carbon atoms through interaction with a metallic nanostructure. The prepared structure, made of a nano slot antenna and a nano island located at the center, acts as a nanogap capacitor and enhances the local electric field by two orders of magnitudes thereby causing the ionization of ambient carbon atoms. Ionization and accumulation of carbon atoms are also observed through the change of the resonant condition of the nano slot antenna and the shift of the characteristic mode in the spectrum of the transmitted THz waves.

Synergistic antitumor effects of combination treatment with metronomic doxorubicin and VEGF-targeting RNAi nanoparticles

ABSTRACT Conventional cancer treatment strategies have been aimed at eradicating all cancer cells. To this end, standard chemotherapeutic approaches have relied on the maximum tolerated dose (MTD) of cytotoxic drugs with a long off‐therapy interval, leading to heavy toxic side effects accompanied by drug resistance. To avoid the problems associated with the traditional MTD chemotherapy, metronomic chemotherapy with relatively low dose continuous treatments of cytotoxic drugs has been proposed as an alternative to the predominant paradigm of directly killing all cancer cells. Low‐dose metronomic (LDM) chemotherapy is expected to have not only antitumor effects without toxicity and drug resistance, but also beneficial anti‐angiogenic effects by causing selective apoptosis of tumor endothelial cells. In an attempt to keep the drug resistance under control and halt exponential tumor growth, herein, we combined LDM chemotherapy with a second anti‐angiogenic strategy. The selective blockade of vascular endothelial growth factor (VEGF) in combination with metronomic doxorubicin (Dox) induced synergistic antitumor effects mainly through an antiangiogenic mechanism. For specific VEGF suppression, VEGF‐targeting siRNA was delivered to tumor tissue using polymerized siRNA/thiolated glycol chitosan (poly‐siVEGF/tGC) nanoparticles, leading to efficient VEGF gene knockdown in tumor tissue with a sequence‐specific manner. Although the single treatment with metronomic Dox and poly‐siVEGF/tGC nanoparticles alone showed some antitumor activity, notably, the combination of the two therapies resulted in superb tumor regression without causing systemic toxicity or drug resistance. Thus, these results suggest that the VEGF‐targeted RNAi using poly‐siRNA/tGC nanoparticles in combination with LDM chemotherapy could be a promising synergistic strategy for controlling tumor growth by enhancing the efficacy of anti‐angiogenesis while minimizing toxicity and drug resistance. Graphical abstract Figure. No caption available.

Simultaneous regulation of apoptotic gene silencing and angiogenic gene expression for myocardial infarction therapy: Single-carrier delivery of SHP-1 siRNA and VEGF-expressing pDNA

Gene therapy is aimed at selectively knocking up or knocking down the target genes involved in the development of diseases. In many human diseases, dysregulation of disease-associated genes is occurred concurrently: some genes are abnormally turned up and some are turned down. In the field of non-viral gene therapy, plasmid DNA (pDNA) and small interfering RNA (siRNA) are suggested as representative regulation tools for activating and silencing the expression of genes of interest, representatively. Herein, we simultaneously loaded both siRNA (Src homology region 2 domain-containing tyrosine phosphatase-1 siRNA, siSHP-1) for anti-apoptosis and pDNA (hypoxia-inducible vascular endothelial growth factor expression vector, pHI-VEGF) for angiogenesis in a single polymeric nanocarrier and used to synergistically attenuate ischemia-reperfusion (IR)-induced myocardial infarction, which is mainly caused by dysregulating of cardiac apoptosis and angiogenesis. For dual-modality cardiac gene delivery, siSHP-1 and pHI-VEGF were sequentially incorporated into a stable nanocomplex by using deoxycholic acid-modified polyethylenimine (DA-PEI). The resulting DA-PEI/siSHP-1/pHI-VEGF complexes exhibited the high structural stability against polyanion competition and the improved resistance to digestion by nucleases. The cardiac administration of DA-PEI/siSHP-1/pHI-VEGF reduced cardiomyocyte apoptosis and enhanced cardiac microvessel formation, thereby reducing infarct size in rat ischemia-reperfusion model. The simultaneous anti-apoptotic and angiogenic gene therapies synergized the cardioprotective effects of each strategy; thus our dual-modal single-carrier gene delivery system can be considered as a promising candidate for treating ischemic heart diseases.

Artificial Rod and Cone Photoreceptors with Human-Like Spectral Sensitivities

Photosensitive materials contain biologically engineered elements and are constructed using delicate techniques, with special attention devoted to efficiency, stability, and biocompatibility. However, to date, no photosensitive material has been developed to replace damaged visual-systems to detect light and transmit the signal to a neuron in the human body. In the current study, artificial nanovesicle-based photosensitive materials are observed to possess the characteristics of photoreceptors similar to the human eye. The materials exhibit considerably effective spectral characteristics according to each pigment. Four photoreceptors originating from the human eye with color-distinguishability are produced in human embryonic kidney (HEK)-293 cells and partially purified in the form of nanovesicles. Under various wavelengths of visible light, electrochemical measurements are performed to analyze the physiological behavior and kinetics of the photoreceptors, with graphene, performing as an electrode, playing an important role in the lipid bilayer deposition and oxygen reduction processes. Four nanovesicles with different photoreceptors, namely, rhodopsin (Rho), short-, medium-, and longwave sensitive opsin 1 (1SW, 1MW, 1LW), show remarkable color-dependent characteristics, consistent with those of natural human retina. With four different light-emitting diodes for functional verification, the photoreceptors embedded in nanovesicles show remarkably specific color sensitivity. This study demonstrates the potential applications of light-activated platforms in biological optoelectronic industries.

Highly sensitive terahertz sensor for glucose detection

In this report, we present a new type of non-contact detection method for glucose molecule using nano antenna array based bio sensing chip that operates at terahertz frequency range (0.5 – 2.5 THz). Localized and hugely enhanced transmitted terahertz field by nano antenna array in the sensing chip induced enhancement of absorption coefficient of glucose molecule that enables us to detect even very small volume of molecules. Nano antenna based terahertz sensing chip can be expected to offer accurate identification of glucose level as a non-invasive and painless sensing tool with high sensitivity.

Development of Biocompatible HA Hydrogels Embedded with a New Synthetic Peptide Promoting Cellular Migration for Advanced Wound Care Management

Abstract In the past few years, there have been many efforts underway to develop effective wound healing treatments for traumatic injuries. In particular, wound‐healing peptides (WHPs) and peptide‐grafted dressings hold great promise for novel therapeutic strategies for wound management. This study reports a topical formulation of a new synthetic WHP (REGRT, REG) embedded in a hyaluronic acid (HA)‐based hydrogel dressing for the enhancement of acute excisional wound repair. The copper‐free click chemistry is utilized to form biocompatible HA hydrogels by cross‐linking dibenzocyclooctyl‐functionalized HA with 4‐arm poly(ethylene glycol) (PEG) azide. The HA hydrogels are grafted with the REG peptide, a functional derivative of erythroid differentiation regulator1, displaying potent cell motility‐stimulating ability, thus sustainably releasing physiologically active peptides for a prolonged period. Combined with the traditional wound healing benefits of HA, the HA hydrogel embedded REG (REG‐HAgel) accelerates re‐epithelialization in skin wound healing, particularly by promoting migration of fibroblasts, keratinocytes, and endothelial cells. REG‐HAgels improve not only rate, but quality of wound healing with higher collagen deposition and more microvascular formation while being nontoxic. The peptide‐grafted HA hydrogel system can be considered as a promising new wound dressing formulation strategy for the treatment of different types of wounds with combinations of various natural and synthetic WHPs.

MicroRNA-mediated non-viral direct conversion of embryonic fibroblasts to cardiomyocytes: comparison of commercial and synthetic non-viral vectors

Abstract Technological advances opened up new ways of directing cell fate conversion from one cell lineage to another. The direct cell conversion technique has recently attracted much attention in regenerative medicine to treat devastated organs and tissues, particularly having limited regenerative capacity such as the heart and brain. Unfortunately, its clinical application is severely limited due to a safety concern and immunogenicity of viral vectors, as human gene therapy did in the beginning stages. In this study, we examined the possibility of adopting non-viral vectors to direct cell conversion from mouse embryonic fibroblasts to induced cardiomyocytes (iCM) by transient transfection of four types of chemically synthesized micro-RNA mimics (miRNA-1, 133, 208, and 499). Herein, we tested several commercial and synthetic non-viral gene delivery carriers, which could be divided into three different categories: polymers [branched PEI (bPEI), bioreducible PEI (PEI-SS), deoxycholic acid-conjugated PEI (DA-PEI), jetPEI™, SuperFect™], lipids (Lipofectamine 2000™), and peptides (PepMute™). According to the analyses of physicochemical properties, cellular uptake, and cytotoxicity of the carrier/miRNA complexes, DA-PEI exhibited excellent miRNA delivery efficiency to mouse embryonic fibroblasts. One week after a single treatment of DA-PEI/miRNA without other adjuvants, the cells started to express cardiomyocyte-specific markers, such as α-actinin and α-MHC, indicating the formation of cardiomyocyte-like cells. Although the overall frequency of non-viral vector induced cardiomyogenic transdifferentiation was quite low (ca. 0.2%), this study can provide compelling support to develop clinically applicable transdifferentiation techniques.

Generation of Broadband Supercontinuum through Nonlinear Interaction in DNA Materials

We demonstrated supercontinuum generation through DNA materials. The DNA material, which is modified copper ion, provided optical nonlinearity within a hollow optical fiber. The supercontinuum spectrum is optimized by fiber length and copper ion concentration for the bandwidth of more than 800nm.