Joon Myong SongSeoul National University | SNU · College of Pharmacy
Joon Myong Song
Doctor of Philosophy
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175
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August 2001 - February 2004
September 2013 - October 2015
Publications
Publications (175)
The advent of precision medicine in oncology emphasizes the urgent need for innovative therapeutic strategies that effectively integrate diagnosis and treatment while minimizing invasiveness. Manganese oxide nanomaterials (MONs) have emerged as a promising class of nanocarriers in biomedicine, particularly for targeted drug delivery and the therape...
Aflatoxin B1, found in a variety of foods, is a mycotoxin known to cause cancer. Therefore, humans may be exposed to it through their daily diet. In this study, a three-dimensional (3D) tumor spheroid model was developed via 3D bioprinting to examine whether exposure of HepG2 liver tumor spheroids to aflatoxin B1 can increase the population of drug...
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have improved the survival of non small cell lung cancer (NSCLC) patients with active mutation of EGFR. However, some of the patients who received EGFR-TKIs showed the acquired resistance, and eventually relapsed within several months. In the TCGA data sets, gene expression of...
Cancer stem cells (CSCs), also known as tumor-initiating cells, are critically correlated with carcinogenesis and are strongly affected by the environmental factors. Environmental carcinogens, such as benzo(a)pyrene (BaP), are associated with the overproduction of CSCs in various types of cancers, including breast cancer. In this report, we present...
In this study, we elucidated for the first time the role of anti-cancer drugs in transarterial chemoembolization (TACE) via direct visualization of the spatial distribution of drugs with respect to blood vessels in intact transparent hepatocellular carcinoma (HCC) tissues. To date, precise estimation of drug penetration into tumors using thin 3D ti...
The development of new in vitro models that closely mimic the tumor microenvironment (TME) to evaluate the efficacy of anticancer drugs has received great attention. In this study, a three-dimensional (3D) bioprinted Michigan Cancer Foundation-7 (MCF-7) cancer spheroid-embedded hydrogel model was suggested for integrative in situ determination of t...
3D bioprinted cardiac constructs have the potential to develop into functional native tissue. Although bioengineered cardiac constructs can be a promising tool for evaluating cardiac responses, the intrinsic limitation in reproducing the well-defined structural and functional properties of native cardiac tissue within the generated substitute restr...
Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related deaths worldwide. Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage HCC. While TACE has been widely used for the treatment of HCC, there are unsolved questions on the use...
Drug-resistant cancer spheroids were fabricated by three-dimensional (3D) bioprinting for the quantitative evaluation of drug resistance of cancer cells, which is a very important issue in cancer treatment. Cancer spheroids have received great attention as a powerful in vitro model to replace animal experiments because of their ability to mimic the...
3D spheroid cultures are attractive candidates for application in in vitro drug-induced hepatotoxicity testing models to improve the reliability of biological information obtainable from a simple 2D culture model. Various 3D spheroid culture models exist for hepatotoxicity screening, but quantitative assays of spheroid response in situ are still ch...
Three-dimensional (3D) visualization of tumor vasculature is a key factor in accurate evaluation of RNA interference (RNAi)-based antiangiogenic nanomedicine, a promising approach for cancer therapeutics. However, this remains challenging because there is not a physiologically relevant in vitro model or precise analytic methodology. To address this...
Silver sulfide quantum dots (Ag2S QDs) as a theragnostic agent have received much attention because they provide excellent optical and chemical properties to facilitate diagnosis and therapy simultaneously. Ag2S QDs possess brightness and photostability suitable for intense and stable bioimaging. It has been verified via in vitro and in vivo studie...
Antioxidants are essential in regulating various physiological functions and oxidative deterioration. Over the past decades, many researchers have paid attention to antioxidants and studied the screening of antioxidants from natural products and their utilization for treatments in diverse pathological conditions. Nowadays, as printing technology pr...
Background:
In this study, a multifunctional tetraphenylporphyrin (TPP) conjugated polyethylene glycol with biotin (TPP-PEG-biotin) as a photo-dynamic therapy (PDT) material encapsulating a ruthenium complex 1 (Ru-1) was fabricated as self-assembled nanoparticle (Ru-1@TPP-PEG-biotin SAN) to co-target glucose-regulated protein 78 (GRP78) and the ly...
Passive targeting of nanoparticles (NPs) mediated by Enhanced Permeability and Retention effect is essential to NP delivery to tumors. However, clinically, only limited success has been found due to inadequate intratumoral delivery. Herein, for the first time, we present direct a demonstration visualizing the spatial distribution of liposomal nanop...
Novel bis-naphthalimide (NI)-based molecules composed of a space linker (bis-NI1, bis-NI2: phenyl dialkyne/ bis-NI3, bis-NI4: triazole/ bis-NI5, bis-NI6: alkyne) with the distinctive side chain of 2,6-diisopropylaniline or 2,4,6-trimethylaniline were designed and synthesized as nanoparticles (NPs) that bind to G-quadruplex (G4) DNA. The supramolecu...
In this study, an inkjet bioprinting-based high-throughput screening (HTS) system was designed and applied for the first time to a catecholpyrimidine-based small molecule library to find hit compounds that inhibit c-Jun NH2-terminal kinase1 (JNK1). JNK1 kinase, inactivated MAPKAPK2, and specific fluorescent peptides along with bioink were printed o...
Fluorescence resonance energy transfer (FRET) is widely used for the detection of a target interaction in biomolecular and cellular research. Based on the sensitivity of the FRET, various innovative analytical biosensors are being developed. This review presents the current status of the use of printing technology with FRET-related applications. Pr...
In this study, we described a novel method to detect the kinase-to-kinase phosphorylation cascade reaction using a commercially available inkjet printing machine. It is very difficult to accomplish the kinase phosphorylation cascade reaction with inkjet printing because of the complex optimization of various reaction conditions inherent to transien...
A graphene oxide (GO)-based cost-effective, automatted strip test has developed for screening of inhibitors of endonuclease EcoRV. The method involves the use of GO and a DNA substrate for EcoRV that contains both an ssDNA region for binding of GO and a fluorescein amidite (FAM)-labelled dsDNA. All the components were inkjet printed on a piece of p...
The combination of chemotherapy and photodynamic therapy (Chemo-PDT) has been suggested as an alternative therapy for drug-resistant cancers. In this study, biotin-conjugated PEGylated photosensitizer (PS) self-assembled nanoparticles (meso-tetraphenylporphyrin (TPP)-PEG-Biotin SANs) were prepared by a self-assembly process to serve as nanocarrier...
Auto neuronal synapses, or autapses, are aberrant structures where the synaptic contact of a neuron forms onto its own branch. The functions of autapses, however, remain unknown. Here, we introduce a simple patterning method for capturing a single-cell, in which we maintained the isolated cell until it reached maturity, and developed arrays of auta...
MicroRNAs (miRNAs) are important regulatory RNAs that control gene expression in various biological processes. Therefore, control over the disease-related miRNA expression is important both for basic research and for a new class of therapeutic modality to treat serious diseases such as cancer. Here, we present a high-throughput screening strategy t...
Ruthenium(II/III) metal complexes have been widely recognized as the alternative chemotherapeutic agents to overcome the drug resistance and tumor recurrence associated with platinum derivatives. In this work, a novel ruthenium(II) triazine complex namely, 1 ([Ru(bdpta)(tpy)]2+) was synthesized and spectroscopically characterized. Drug resistant ca...
Degradation of cyclic adenosine mono phosphate (cAMP) by phosphodiesterase-4B (PDE-4B) in the inflammatory cells leads to elevated expression of inflammatory cytokines in inflammatory cells. Suppression of cytokines has proved to be beneficial in the treatment of atopic dermatitis (AD). Henceforth, application of PDE4B specific inhibitor to minimiz...
The statement of significance:
Microvascular networks are not only biological system constituting largest surface area in the body and but also first site exposed to nanoparticle in vivo. While cationic polymer NPs have been intensively studied as non-viral delivery systems, its biological effects in human microvessel have been poorly investigated...
Amyloid-β (Aβ) is generated by proteolytic processing of amyloid precursor protein (APP) by beta-secretase (BACE-1) and gamma-secretase. Amyloid-β is responsible for the formation of senile plaques in Alzheimer's disease (AD). Consequently, inhibition of β-secretase (BACE-1), a rate-limiting enzyme in the production of Aβ, constitutes an attractive...
The most common therapy for estrogen receptor-positive breast cancer is anti-hormone therapy such as tamoxifen (TAM). However, acquisition of resistance to TAM in one-third of patients presents a serious clinical problem. Polo-like kinase 1 (Plk1) is a key oncogenic regulator of completion of G2/M phase of the cell cycle. We assessed Plk1 expressio...
In this study, we report the photo-induced electron transfer (PET) on parchment paper using riboflavin as a photo inducer and ultraviolet lamp (362 nm) as the light source. To this end, a conventional inkjet printer equipped with 4 cartridges was used. Parchment paper was found to be a favorable substrate due to its insignificant self-absorption wh...
The antibacterial properties of silver nanoparticles (AgNPs) depends on the valence form of the silver ion. It is well established that the higher valent silver ion showed better antibacterial activity than the lower valent silver ion. The higher valent, monodisperse nanoparticles of silver chlorhexidine and silver-pyridoxine complex were synthesiz...
For the first time, a paper-based fluorescence resonance energy transfer (FRET) determination with cyclic AMP (cAMP)-specific phosphodiesterase 4B (PDE4B) inhibitory assay using an inkjet-printing technique is proposed. Non-fabricated parchment paper is found to constitute a unique substrate to measure fluorescent energy transfer, due to its insign...
Resistance to chemotherapy is a key factor in the inefficacy of various forms of treatments for cancer. In the present study, chemo-resistant proteins, including glucose-regulated protein 78 (GRP78)/clusterin (CLU) targeted 1,2-dioleoyloxy-3-trimethylammoniumpropane (DOTAP) liposomes, were developed as a delivery system for co-delivery of camptothe...
Fluorescent Au nanocrystals-silica hybrid nanocomposite (FLASH) was synthesized by co-condensation of surface modified Au nanocrystals (AuNCs). Present FLASH nanocomposite exhibited 4 times enhanced photoluminescence and photocatalytic activity compared to single nanocrystals. Based on these enhanced optical features, we successfully demonstrated i...
Selective inhibition of phosphodiesterase (PDE) 4B favorably suppresses the synthesis of inflammatory cytokines and subsequently arrest the development of atopic dermatitis via modulating the intracellular cAMP levels. Considering the side effects of corticosteroids, selective PDE4 inhibition could constitute an effective alternative therapy for th...
A peptide probe-based MMP-9 inhibitory assay was developed to assess anticancer activity of compounds on parchment paper using FRET-based inkjet printing. The fluorescent peptide containing 5-FAM (donor) and QXL520 (acceptor) was used as a substrate with the sequence of Pro-Leu-Gly-Cys-His-Ala-Arg-Lys specific to MMP-9. The suitability of the pepti...
An improved cell conversion strategy for neural differentiation of mouse embryonic stem (mES) cells is developed by incorporating functionalized mesoporous silica nanoparticle (MSN) as an efficient delivery carrier of retinoic acid (RA), which is pleiotropic factor required for initiation of neural differentiation. Traditional RA-mediated neural di...
Diabetic foot ulcer (DFU) is becoming more serious concern as it affects 95% of diabetic patients worldwide. It has been shown that the Staphylococcus aureus and other Gram-negative microorganisms are the main reasons behind this disease. Though many antibiotics are presently used to treat the DFU, due to increased bacterial resistance, new alterna...
Primary cell cultures mimic the physiology and genetic makeup of in-vivo tissue of origin, nonetheless, a complication in the derivation and propagation of primary cell culture limits its use in biological research. However, in-vitro models using primary cells might be a complement model to mimic in vivo response. But, conventional techniques such...
The existence of a well-established drug resistance mechanism in cancer stem cells (CSC) complicates the cancer treatment. Clusterin (CLU) plays a key role in maintaining the integrity of endoplasmic reticulum (ER) during drug-induced stress. Hence, silencing the CLU could significantly reduce the inherent drug resistance mechanism of CSC. The comb...
Antiretroviral treatment can reduce the death rate of human immunodeficiency virus (HIV) infection, and its effectiveness is maximized at the early stage of HIV infection. The present protocol demonstrates an early stage high-content HIV diagnosis based on multicolor concurrent monitoring of CD4, CD8, and CD3 coreceptors and F-actin cytoskeleton us...
Cadmium, a heavy metal pollutant, causes cancer. The existence of cancer stem cells (CSCs) in tumors is widely considered to be the reason for the recurrence and treatment failure of cancer. Increasing evidence has confirmed that under certain conditions non-CSCs could be converted into CSCs. The impact of cadmium on the development of CSC lineage...
Photodynamic therapy (PDT) is a non-chemo drug approach for the killing of different type of cancers. PDT is a light-activated cancer therapy, it involves the use of light source, photosensitizer, and intracellular molecular oxygen and water. Reactive oxygen species are usually produced due to the interaction between photosensitizer and molecular o...
An accurate, rapid, and cost-effective methodology for enzyme inhibitor assays is highly needed for large-scale screening to evaluate the efficacy of drugs at the molecular level. For the first time, we have developed an inkjet printing-based enzyme inhibition assay for the assessment of drug activity using a conventional inkjet printer composed of...
Cancer is becoming one of the leading causes of death in the world. In photodynamic therapy (PDT), highly reactive oxygen species (ROS) is usually produced to treat cancer by interaction of light with a PDT agent usually called photosensitizer (PS) and dissolved molecular oxygen. The therapeutic properties of light have been known for thousands of...
5,10,15,20-Tetrakis(benzo[b]thiophene) porphyrin (BTP) is a newly synthesized hydrophobic photosensitizer with fluorescence quantum yield in toluene: ΦF = 0.062. Previously, its limitations in solubility had hindered scientific experimentation regarding its photodynamic effects on cancer cells. By utilizing various compositions of liposomes in orde...
Elevated expression of drug efflux pumps such as multidrug resistant protein-1 (MDR1/ABCB1) and multidrug resistance associated protein-1 (MRP1/ABCC1) in cancer stem cells (CSCs) among a bulky tumor cell population was attributed to drug resistance. For the first time, we have quantitatively evaluated the cytotoxic profile of camptothecin (CPT) aga...
Elevated expression of epidermal growth factor receptor (EGFR) is reported to be associated with poor prognosis in breast cancer. EGFR subtype identification plays a crucial role in deciding the drug combination to treat the cancer patients. Conventional application of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) produce...
We report a two color monitoring of drug-induced cell deaths using total internal reflection fluorescence (TIRF) as a novel method to determine anticancer activity. Instead of cancer cells, breast cancer stem cells (CSCs) were directly tested in the present assay to determine the effective concentration (EC50 ) values of camptothecin and cisplatin....
The antibacterial and moisturizing effects inherent to silver nanoparticles contribute greatly to their use as a topical antibacterial agent. The antibacterial property of silver nanoparticles provides topical wounds with an indirect environment for healing through the prevention of pathogenic infection. However, the direct wound-healing effects of...
Insulin signalling causes the translocation of glucose transporter 4 (GLUT4) to the plasma membrane to facilitate cellular glucose uptake. Numerous observations indicate that the prime cause of type 2 diabetes mellitus (T2DM) is inflammation, the occurrence of which increases in obese individuals. Inflammatory mediators induce an insulin-resistance...
Semiconductor quantum dots (QD) possess unique optical and electric properties like size-tunable light emission, narrow emission range, high brightness and photostability. Recent research advances have minimized the toxicity of QDs and they are successfully used in in vitro and in vivo imaging. Encapsulation of QDs into polymeric nanoparticles and...
Cancer stem cells (CSCs), known as tumor initiating cells, have become a critically important issue for cancer therapy. Although much research has demonstrated the induction of hepato cellular carcinoma by aflatoxin B1, the formation of hepatocellular CSCs and their quantitative determination is hardly reported. In this work, it was found that hepa...
Advancements in nano-structured materials have facilitated several applications of nanoparticles (NPs). Skin penetration of NPs is a crucial factor for designing suitable topical antibacterial agents with low systemic toxicity. Available reports focus on size-dependent skin penetration of NPs, mainly through follicular pathways. Herein, for the fir...
Silver nanoparticles (AgNPs) are capable of inhibiting the growth of a broad spectrum of bacterial species. The minute size of the nanoparticulates enhances their biocidal activity and is thus widely utilized as antibacterial agents. The most recently researched and recognized antibacterial and wound-healing properties of published AgNPs were inves...
Breast cancer is the major cause of cancer death for women worldwide. Breast cancer patients are treated with chemotherapy and radiotherapy. Although chemotherapy and radiotherapy are applied, some cancer cells still survive. These cells, called cancer stem cell (CSC), exhibit special capabilities, such as drug and radio resistance. The remaining C...
Photodynamic therapy (PDT) selectively targets subcellular organelles and promises an excellent therapeutic strategy for cancer treatment. Here, we report the synthesis of a new water-soluble photosensitizer, 5, 10, 15, 20-Tetrakis (7-sulfonatobenzo[b]thiophene) Porphyrin (SBTP). Rational design of the porphyrinic molecule containing Benzo[b]thioph...
Even with the prevalence of wounds, the medical technology for efficiently managing skin damage is still primitive. The disruption of any of the numerous healing processes can lead to problems in the time-sensitive healing actions of the dermal and epidermal layers. Bacterial infection is one of the major obstacles to proper wound healing as it pos...
Cellular inflammation is a non-specific immune response to tissue injury that takes place via cytokine network orchestration to maintain normal tissue homeostasis. However chronic inflammation that lasts for a longer period, plays the key role in human diseases like neurodegenerative disorders and cancer development. Understanding the cellular and...
With advancements in nanotechnology, silver has been engineered into a nanometre size and has attracted great research interest for use in the treatment of wounds. Silver nanoparticles (AgNPs) have emerged as a potential alternative to conventional antibiotics because of their potential antimicrobial property. However, AgNPs also induce cytotoxicit...
TNF-α is an inflammatory cytokine that plays an important role in insulin resistance observed in obesity and chronic inflammation. Many cellular components involved in insulin signaling cascade are known to be inhibited by TNF-α. Insulin receptor substrate (IRS)-1 is one of the major targets in TNF-α-induced insulin resistance. The serine phosphory...
In this study, it was found that breast cancer stem cells (CSCs) are formed from MCF-7 cells by benzo[a]pyrene (BP)-induced mutation. The breast CSCs were detected through simultaneous monitoring of CD44, CD24 and aldehyde dehydrogenase 1 (ALDH1) by hypermulticolor cellular imaging using an acousto-optical tunable filter (AOTF) and quantum dots (Q-...
The circulating endothelial progenitor cells (EPCs) in blood of acute myocardial infarction (AMI) patient have been monitored in many previous studies. The number of circulating EPC increases in the blood of patients at onset of the AMI. EPC is originated from bone marrow. It performs vessel regeneration. There are many markers used for detecting E...
The present study relates to a combined killing and healing approach for the treatment of infected wounds. Herein we report a multifunctional, including antimicrobial and wound healing, composite containing a conjugate of a bi-valent silver polydiguanide that demonstrated high antibacterial activity in vitro and a potent wound healing polypeptide,...
A regional average intensity-based adherent cellular imaging assay has been applied to the evaluation of drug-induced cardiotoxicity. Unlike single cell imaging cytometry, which requires isolated single cells, regional average intensity-based cellular imaging does not require enzymatic treatment for the detachment and isolation of adherent cells. I...
Anti-retroviral treatment can reduce the death rate of human immunodeficiency virus (HIV) infection and its effectiveness is maximized at the early stage of HIV infection. The present study demonstrates an early stage high-content HIV diagnosis based on multicolor concurrent monitoring of CD4, CD8, CD3 coreceptors, and F-actin cytoskeleton using qu...
Cardiac action potential abnormalities are a major cause of Torsades de pointes (TdP) and even sudden cell death. Cardiac dysfunction can be induced by drugs and a lot of pharmaceuticals have been withdrawn from the market due to their unexpected cardiotoxicity. It has recently been noticed that in vitro screening of drug-induced cardiotoxicity has...
There is a growing interest in alopecia prevention strategies, as the number of alopecia patients is increasing. We examine the efficacy of herbal medicine for hair growth promotion/hair loss inhibition in two cell lines via Western blot and high-content screening (HCS). Nine herbal extracts were obtained from three different herbal medicine mixtur...
The aim of this study was to investigate whether the results of segmental hair analysis can be used to estimate patterns of methamphetamine (MA) use. Segmental hair analysis for MA and amphetamine (AP) was performed. Hair was cut into the hair root, consecutive 1 cm length segments and 1-4 cm length segments. Whole hair was also analyzed. The hair...
A quantitative high-content screening (HCS) was suggested for the real-time monitoring of drug-induced mitochondrial dysfunction-mediated hepatotoxicity. This HCS is very advantageous in that it allows simultaneous observation of drug-induced activations of hepatotoxic pathways using hypermulticolor cellular imaging. The mitochondrial permeability...
Successful therapeutic modalities against breast cancer (BC) are highly dependent on the accurate prognosis and quantitative simultaneous classification of BC subtypes. Current methods based on semi-quantitative analysis or subjective interpretations are not efficient for BC prognosis and classification considering tumor heterogeneity. In this work...
Although human lysyl-tRNA synthetase (KRS), an enzyme for protein synthesis, is often highly expressed in various cancer cells, its pathophysiological implications have not been understood. Here we found that KRS induces cancer cell migration through interaction with the 67-kDa laminin receptor (67LR) that is converted from ribosomal subunit p40. O...
Forensic DNA samples can degrade easily due to exposure to light and moisture at the crime scene. In addition, the amount of DNA acquired at a criminal site is inherently limited. This limited amount of human DNA has to be quantified accurately after the process of DNA extraction. The accurately quantified extracted genomic DNA is then used as a DN...
Cannabis is the most widely abused drug in the world. The purpose of this study is to detect 11-nor-9-carboxy-Δ⁹-tetrahydrocannabinol (THCCOOH) in segmental hair and to evaluate the patterns of cannabis use. We investigated the relationship between the concentrations of THCCOOH in hair and the self-reported use data and the route of administration....
Multi-target-multi-drug approaches are needed to accelerate the process of drug discovery screening and to design efficient therapeutic strategies against diseases that involve alterations in multiple cellular targets. Herein we report single-cell cotransfection imaging cytometry to quantitatively screen drug-induced off-target effects. Vascular en...
In this study, the concentrations of 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in pubic, axillary and beard hair were measured and the correlation between the concentrations of THCCOOH in head and pubic hair from same cannabis users were evaluated. The papers on body hair analysis for THCCOOH were rarely found although police off...
The present study describes a gas chromatography/tandem mass spectrometry-negative ion chemical ionization assay (GC/MS/MS-NCI) for simultaneous analysis of Δ(9)-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) in hair. Each hair sample, of approximately 20mg, was weighed and the sample was dissolved in 1ml of 1M sodiu...
Effects of UVB or UVC-induced DNA damage were simultaneously monitored at single cellular level by analyzing the change of yellow fluorescent protein (YFP) and red fluorescent protein (RFP) expression in human embryonic kidney (HEK) 293 cells using multicolor single-cell imaging cytometry. The method is based on the idea that there exists a quantit...
Implementation of proper analytical tool for systematic investigation and quantitative determination of different classes of cadmium ion-induced DNA damages, especially at low metal ion concentrations, is still lacking. Using lesion-specific enzymes that cleave DNA at specific classes of damage and a fluorometric approach developed for quantifying...
Understanding the role of oncomirs allows new insights into the development of modern therapeutic approaches for the repression of multiple oncomirs in cancer cells. At present, no suitable approach is available to repress the development of multiple oncomirs in cancer cells. Herein, we report that argonaute 2 (AGO2) could be a unique molecule to r...