Publications by authors named "Dal-Hee Min"

102 Publications

Synthesis of gold nano-mushrooms solvent-controlled galvanic replacement to enhance phototherapeutic efficiency.

Nanoscale 2022 Jan 12. Epub 2022 Jan 12.

Department of Chemistry, Kwangwoon University, 20, Gwangwoon-ro, Nowon-gu, Seoul 01897, Republic of Korea.

In advanced galvanic replacement, variable factors such as the combination of two elements where actual redox reaction and post-synthetic structural transformation take place. Research on manufacturing distinctive nanostructures has mainly focused on the shape of the sacrificial nanotemplate, the presence or absence of additives, and the reaction temperature. Here, we have attempted to confirm the dependency on the solvent, which was considered to simply serve as a medium for a homogeneous chemical reaction to proceed by aiding the dispersion of the nanotemplate and reactants. Thus, we obtained mushroom-like Au nanoplates (mAuNPs) by comprehensive galvanic replacement reaction between solvents, additives, and adsorbents. The mAuNPs with a porous Au nanoplate head and a hollow nanotube tail structure were formed an optimization process in a 50 v/v% solvent comprising water and ethylene glycol. As a result of confirming the galvanic replacement in co-solvent conditions, in which various types of water miscible solvents were introduced, it was revealed that the most critical factors for regulating the surface polymeric environment of the nanoplate were the relative polarity index of the co-solvent and the hydrogen bonding type. These depend on the molecular structure of the solvent. The manufactured mAuNPs exhibited excellent absorbance in the near-infrared region, and efficient photothermal (PT) conversion-mediated heat dissipation under local laser irradiation. These results confirm the viability of the gene-thermo dual-modal combinatorial cancer therapy based on the surface loading of oligonucleotides and peptides, and the PT therapeutic approach and .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1nr06634jDOI Listing
January 2022

Nanoparticle delivery of recombinant IL-2 (BALLkine-2) achieves durable tumor control with less systemic adverse effects in cancer immunotherapy.

Biomaterials 2022 Jan 19;280:121257. Epub 2021 Nov 19.

Institute of Biotherapeutics Convergence Technology, Lemonex Inc., Seoul, 06683, Republic of Korea. Electronic address:

Recent strategies in cancer immunotherapy based on interleukin-2 (IL-2) are generally focused on reducing regulatory T cell (Treg) development by modifying IL-2 receptor alpha (IL-2Rα) domain. However, the clinical utility of high-dose IL-2 treatment is mainly limited by severe systemic toxicity. We find that peritumorally injectable 'BALLkine-2', recombinant human IL-2 (rIL-2) loaded porous nanoparticle, dramatically reduces systemic side effects of rIL-2 by minimizing systemic IL-2 exposure. Notably, in cynomolgus monkeys, subcutaneous (SC)-injection of BALLkine-2 not only dramatically reduces systemic circulation of rIL-2 in the blood, but also increases half-life of IL-2 compared to IV- or SC-injection of free rIL-2. Peritumorally-injected BALLkine-2 enhances intratumoral lymphocyte infiltration without inducing Treg development and more effectively synergizes with PD-1 blockade than high-dose rIL-2 administration in B16F10 melanoma model. BALLkine-2 could be a highly potent therapeutic option due to higher anti-tumor efficacy with lower and fewer doses and reduced systemic toxicity compared to systemic rIL-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2021.121257DOI Listing
January 2022

Osmium-Tellurium Nanozymes for Pentamodal Combinatorial Cancer Therapy.

ACS Appl Mater Interfaces 2021 Sep 8;13(37):44124-44135. Epub 2021 Sep 8.

Department of Chemistry, Kwangwoon University, 20 Gwangwoon-ro, Nowon-gu, Seoul 01897, Republic of Korea.

Although nanoparticles based on Group 8 elements such as Fe and Ru have been developed, not much is known about Os nanoparticles. However, Os-based nanostructures might have potential in various applications including biomedical fields. Therefore, in this study, we synthesized Os-Te nanorods (OsTeNRs) by solvothermal galvanic replacement with Te nanotemplates. We explored the nanozymatic activity of the synthesized OsTeNRs and found that they exhibited superior photothermal conversion and photocatalytic activity. Along with chemotherapy (regorafenib) and immunotherapy, the nanozymatic, photothermal, and photodynamic activities of OsTeNRs were harnessed to develop a pentamodal treatment for hepatocellular carcinoma (HCC); and studies demonstrated that the pentamodal therapy could alleviate hypoxia in HCC cells by generating oxygen and reduced unintended drug accumulation in organs. Moreover, bone-marrow toxicity due to regorafenib could be reduced as the drug was released in a sustained manner. Thus, OsTeNRs can be considered as suitable nanotemplates for combinatorial cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c14201DOI Listing
September 2021

Graphene oxide-based fluorescent biosensors and their biomedical applications in diagnosis and drug discovery.

Chem Commun (Camb) 2021 Sep 28;57(77):9820-9833. Epub 2021 Sep 28.

Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.

Graphene oxide (GO), an oxidized derivative of graphene, has received much attention for developing novel fluorescent bioanalytic platforms due to its remarkable optical properties and biocompatibility. The reliable performance and robustness of GO-based biosensors have enabled various applications in the biomedical field including diagnosis and drug discovery. Here, recent advances in the development of GO-based fluorescent biosensors are overviewed, particularly nucleic acid detection and enzyme activity assay. In addition, practical applications in biomarker detection and high-throughput screening are also examined. Lastly, basic design principles and remaining challenges of these types of biosensors are discussed for further progress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc02157eDOI Listing
September 2021

Identification of a Direct-Acting Antiviral Agent Targeting RNA Helicase via a Graphene Oxide Nanobiosensor.

ACS Appl Mater Interfaces 2021 Jun 26;13(22):25715-25726. Epub 2021 May 26.

Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.

Dengue virus (DENV), an arbovirus transmitted by mosquitoes, causes infectious diseases such as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Despite the dangers posed by DENV, there are no approved antiviral drugs for treatment of DENV infection. Considering the potential for a global dengue outbreak, rapid development of antiviral agents against DENV infections is crucial as a preemptive measure; thus, the selection of apparent drug targets, such as the viral enzymes involved in the viral life cycle, is recommended. Helicase, a potential drug target in DENV, is a crucial viral enzyme that unwinds double-stranded viral RNA, releasing single-stranded RNA genomes during viral replication. Therefore, an inhibitor of helicase activity could serve as a direct-acting antiviral agent. Here, we introduce an RNA helicase assay based on graphene oxide, which enables fluorescence-based analysis of RNA substrate-specific helicase enzyme activity. This assay demonstrated high reliability and ability for high-throughput screening, identifying a new helicase inhibitor candidate, micafungin (MCFG), from an FDA-approved drug library. As a direct-acting antiviral agent targeting RNA helicase, MCFG inhibits DENV proliferation in cells and an animal model. Notably, , MCFG treatment reduced viremia, inflammatory cytokine levels, and viral loads in several tissues and improved survival rates by up to 40% in a lethal mouse model. Therefore, we suggest MCFG as a potential direct-acting antiviral drug candidate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c04641DOI Listing
June 2021

A graphene oxide-based fluorescent nanosensor to identify antiviral agents via a drug repurposing screen.

Biosens Bioelectron 2021 Jul 1;183:113208. Epub 2021 Apr 1.

Department of Chemistry, Seoul National University, Seoul, 08826, Republic of Korea; Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea; Institute of Biotherapeutics Convergence Technology, Lemonex Inc., Seoul, 08826, Republic of Korea. Electronic address:

Currently, there are no approved therapeutics for Dengue virus (DENV) infection, even though it can cause fatal complications. Understanding DENV infection and its propagation process in host cells is necessary to develop specific antiviral therapeutics. Here, we developed a graphene oxide-based fluorescent system (Graphene Oxide-based Viral RNA Analysis system, GOViRA) that enables sensitive and quantitative real-time monitoring of the intracellular viral RNA level in living cells. The GOViRA system consists of a fluorescent dye-labeled peptide nucleic acid (PNA) with a complementary sequence to the DENV genome and a dextran-coated reduced graphene oxide nanocolloid (DRGON). When the dye labeled PNA is adsorbed onto DRGON, the fluorescence of the dye is effectively quenched. The quenched fluorescence signal is recovered when the dye labeled PNA forms interaction with intracellular viral RNA in DENV infected host cells. We demonstrated the successful use of the GOViRA platform for high-throughput screening to discover novel antiviral compounds. Through a cell-based high-throughput screening of FDA-approved small-molecule drugs, we identified ulipristal, a selective progesterone receptor modulator (SPRM), as a potent inhibitor against DENV infection. The anti-DENV activity of ulipristal was confirmed both in vitro and in vivo. Moreover, we suggest that the mode of action of ulipristal is mediated by inhibiting viral entry into the host cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2021.113208DOI Listing
July 2021

Fluorometric Viral miRNA Nanosensor for Diagnosis of Productive (Lytic) Human Cytomegalovirus Infection in Living Cells.

ACS Sens 2021 03 2;6(3):815-822. Epub 2021 Feb 2.

Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.

A human cytomegalovirus (HCMV) causes a persistent asymptomatic infection in healthy individuals and possesses unexpected dangers to newborn babies, immunocompromised people, and organ transplant recipients because of stealth transmission. Thus, an early and accurate diagnosis of HCMV infection is crucial for prevention of unexpected transmission and progression of the severe diseases. The standard method of HCMV diagnosis depends on serology, antigen test, and polymerase chain reaction-based nucleic acid detection, which have advantages for each target molecule. However, the serological test for an antibody is an indirect method assuming the past virus infection, and antigen and viral nucleic acid testing demand laborious, complex multistep procedures for direct virus detection. Herein, we present an alternative simple and facile fluorometric biosensor composed of a graphene oxide nanocolloid and fluorescent peptide nucleic acid (PNA) probe to detect the HCMV infection by simply monitoring the virally encoded microRNA as a new biomarker of lytic virus infection. We verify the sensing of HCMV-derived microRNA accumulated within 72 h after HCMV infection and examine the diagnosis of HCMV in living cells. We proceed with the time course and concentration-dependent investigation of hcmv-miRNA sensing in living cells as a direct method of HCMV detection at the molecular level on the basis of an intracellular hcmv-miRNA expression profile and graphene oxide nanocolloid-based simple diagnostic platform. The fluorometric biosensor enables the sequence-specific binding to the target HCMV miRNAs in HCMV-infected fibroblasts and shows the quantitative detection capability of HCMV infection to be as low as 4.15 × 10 immunofluorescence focus unit (IFU)/mL of the virus titer at 48 h post-infection with picomolar sensitivity for HCMV miRNA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssensors.0c01843DOI Listing
March 2021

3D Microfluidic Platform and Tumor Vascular Mapping for Evaluating Anti-Angiogenic RNAi-Based Nanomedicine.

ACS Nano 2021 01 24;15(1):338-350. Epub 2020 Nov 24.

Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea.

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 limitation, a strategy based on 3D microfluidic angiogenesis-on-a-chip and 3D tumor vascular mapping was developed for evaluating RNAi-based antiangiogenic nanomedicine. We developed a microfluidic model to recapitulate functional 3D angiogenic sprouting when co-cultured with various cancer cell types. This model enabled efficient and rapid assessment of antiangiogenic nanomedicine in treatment of hyper-angiogenic cancer. In addition, tissue-clearing-based whole vascular mapping of tumor xenograft allowed extraction of complex 3D morphological information in diverse quantitative parameters. Using this 3D imaging-based analysis, we observed tumor sub-regional differences in the antiangiogenic effect. Our systematic strategy can help in narrowing down the promising targets of antiangiogenic nanomedicine and then enables deep analysis of complex morphological changes in tumor vasculature, providing a powerful platform for the development of safe and effective nanomedicine for cancer therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c05110DOI Listing
January 2021

Non-viral, direct neuronal reprogramming from human fibroblast using a polymer-functionalized nanodot.

Nanomedicine 2021 02 15;32:102316. Epub 2020 Oct 15.

Department of Chemistry, Seoul National University, Seoul, Republic of Korea; Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea; Institute of Biotherapeutics Convergence Technology, Lemonex Inc., Seoul, Republic of Korea. Electronic address:

Among various strategies to treat neurodegenerative disorders, cell replacement therapies have drawn much attention recently. Such a trend led to the increase in demand for the rare and specialized cells, followed by the outburst development of various cell reprogramming strategies. However, several limitations on these conventional methods remain to be solved, including the genetic instability of the viral vectors and the high cytotoxicity or poor performance of the non-viral carriers. Therefore, non-viral methods need to be developed to ensure safe and efficient cell reprogramming. Here, we introduce a polymer-modified nano-reagent (Polymer-functionalized Nanodot, PolyN) for the safe and efficient, non-viral direct cell reprogramming. PolyN facilitated the highly efficient contemporary overexpression of the transgene compared to the conventional reagent. With our nano-reagent, we demonstrated the SOX2-mediated cell reprogramming and successfully generated the neuron-like cell from the human fibroblast.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nano.2020.102316DOI Listing
February 2021

Intrinsic Peroxidase-Mimicking Ir Nanoplates for Nanozymatic Anticancer and Antibacterial Treatment.

ACS Appl Mater Interfaces 2020 Sep 2;12(37):41062-41070. Epub 2020 Sep 2.

Department of Chemistry, Kwangwoon University, 20 Gwangwoon-ro, Nowon-gu, Seoul 01897, Republic of Korea.

The study of inorganic nanozymes to overcome the disadvantages of bio-enzymes, such as the requirement of optimized reaction conditions and lack of durability against environmental factors, is one of the most significant research topics at present. In this work, we comprehensively analyzed the intrinsic peroxidase-like activity of Ir-based nanoparticles, the biological and nanozymatic potentials of which have not yet been explored. These particles were synthesized by the galvanic replacement of Ag nanoplates with Ir. Through the confirmed peroxidase-like activity and hydrogen peroxide decomposition with free radical generation facilitated by these particles, the antibacterial and anticancer effects were successfully verified . The nanozyme-based therapeutic effect observed at concentrations at which these nanoparticles do not show cytotoxicity suggests that it is possible to achieve more precise and selective local treatment with these particles. The observed highly efficient peroxidase-like activity of these nanoparticles is attributed to the partially mixed composition of Ir-Ag-IrO formed through the galvanic replacement reaction in the synthetic process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c10981DOI Listing
September 2020

Discovery of direct-acting antiviral agents with a graphene-based fluorescent nanosensor.

Sci Adv 2020 May 29;6(22):eaaz8201. Epub 2020 May 29.

Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.

Direct-acting agents against viral components are considered as the most promising candidates for the successful antiviral therapeutics. To date, no direct-acting drugs exist for the treatment against dengue virus (DV) infection, which can develop into life-threatening diseases. RNA-dependent RNA polymerase (RdRp), an RNA virus-specific enzyme highly conserved among various viral families, has been known as the broad-range antiviral drug target. Here, we developed an RNA-based graphene biosensor system [RNA nano-graphene oxide system (RANGO)] to enable the fluorescence-based quantitative analysis of the RdRp enzyme activity. We used the RANGO system to a high-throughput chemical screening to identify novel direct-acting antiviral drug candidates targeting DV RdRp from the FDA-approved small-molecule library. RANGO accelerated the massive selection of drug candidates. We found that one of the selected hit compounds, montelukast, showed antiviral activity in vitro and in vivo by directly inhibiting replication of DV and thus relieved related symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aaz8201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259931PMC
May 2020

Large-Scale 3D Optical Mapping and Quantitative Analysis of Nanoparticle Distribution in Tumor Vascular Microenvironment.

Bioconjug Chem 2020 07 15;31(7):1784-1794. Epub 2020 Jun 15.

Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, South Korea.

Nanoparticles (NPs) are a promising carrier for cancer therapeutics. Systemically administered NPs are transported to tumor tissues via the bloodstream, extravasated from microvessels, and delivered to cancer cells. The distribution of NPs in the tumor vascular microenvironment critically determines the therapeutic efficacy of NP-delivered drugs, but its precise assessment in 3D across a large volume remains challenging. Here, an analytical platform-termed OMNIA (for Optical Mapping of Nanoparticles and Image Analysis)-integrating tissue clearing, high-resolution optical imaging, and semiautomated image analysis is presented, which enables accurate, unbiased, and quantitative analysis of the distribution of NPs in relation to the vasculature across a large 3D volume. Application of OMNIA to tumor tissues revealed higher accumulation and more efficient extravasation of NPs in the tumor periphery than the core. Time-course analysis demonstrated that the accumulation of NPs in tumor peaked at 24 h after injection, but the relative distribution of NPs from the vasculature remained remarkably stable over time. Comparisons between 45- and 200-nm-sized NPs showed a lower accumulation of smaller NPs in tumors relative to the liver, yet better vessel permeation. Together, our results demonstrate that OMNIA facilitates precise and reliable evaluation of NP biodistribution, and mechanistic investigations on NP delivery to tumor tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.bioconjchem.0c00263DOI Listing
July 2020

A fluorescent nanobiosensor for the facile analysis of mA RNA demethylase activity.

Chem Commun (Camb) 2020 Apr 26;56(34):4716-4719. Epub 2020 Mar 26.

Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.

RNA demethylase has recently been known to be associated with cancer development but its selective inhibitors as anti-cancer agents have rarely been investigated to date. Herein, we have developed a fluorescent nanobiosensor which enables efficient quantitative analysis of RNA demethylase ALKBH5 activity and shows a high potential for robust inhibitor screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc10054gDOI Listing
April 2020

Nonrecurring Circuit Nanozymatic Enhancement of Hypoxic Pancreatic Cancer Phototherapy Using Speckled Ru-Te Hollow Nanorods.

ACS Nano 2020 04 26;14(4):4383-4394. Epub 2020 Mar 26.

Department of Chemistry, Kwangwoon University, 20 Gwangwoon-ro, Nowon-gu, Seoul 01897, Republic of Korea.

Nanozymatic reactions that produce or consume oxygen (O) or reactive oxygen species (ROS) consist of oxidase, peroxidase, superoxide dismutase (SOD), and catalase-type activity. Although extensive studies were conducted to overcome hypoxia through nanozymatic reactions, the construction of an ideal system is challenging, given that the reactants and products are arranged in a recurring structure for continuous consumption in a full cycle. In this study, speckled Ru-Te hollow nanorods were prepared through solvothermal galvanic replacement against Te nanorod templates with high yield and robustness. From their multicompositional characteristics, nonrecurring peroxidase-SOD-catalase-type nanozymatic properties were identified with photothermal and photodynamic feasibility over a wide range of laser irradiation wavelengths. Owing to the excellent colloidal stability and biocompatibility, the proposed Ru-Te-based nanozymatic platform was highly effective in hypoxic pancreatic cancer phototherapy and by near-infrared laser irradiation mediated photothermal and photodynamic combination treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.9b09974DOI Listing
April 2020

RNAi nanotherapy for fibrosis: highly durable knockdown of CTGF/CCN-2 using siRNA-DegradaBALL (LEM-S401) to treat skin fibrotic diseases.

Nanoscale 2020 Mar 5;12(11):6385-6393. Epub 2020 Mar 5.

Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.

Skin fibrosis occurs in a variety of human diseases but the current anti-fibrosis treatments are not sufficient. One major cause of fibrotic diseases shared across diverse organ fibrosis is uncontrolled overexpression of the connective tissue growth factor (CTGF, also known as CCN2). Here, we examine the anti-fibrotic activity of RNAi therapy utilizing siRNA against CTGF with a new drug delivery system (DDS), 'DegradaBALL', which is based on porous nanoparticles, for durable CTGF gene silencing. DegradaBALL is a modular DDS having many favorable properties for RNA delivery such as effective intracellular uptake, convenient drug loading, biocompatibility, sustained release profile and biodegradability. DegradaBALL loaded with siCTGF, named 'LEM-S401', showed highly durable and effective CTGF gene-silencing in TGF-β induced lung fibrosis and skin fibrosis model cells, A549 and HaCaT, respectively. In addition, LEM-S401 induced knockdown of collagen types I and III, which are excess extracellular matrix components in fibrotic skin in addition to CTGF in the mouse wound healing model. Most importantly, we showed that LEM-S401 effectively inhibited the formation of hypertrophic scars in wound-associated dermal fibrosis mouse models, during both the epidermis recovery and tissue remodeling process. Our findings suggest that LEM-S401 could be a highly potent therapeutic option for skin fibrotic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9nr10305hDOI Listing
March 2020

Correction to "Environmentally Friendly Synthesis of Au-Te-Clustered Nanoworms via Galvanic Replacement for Wavelength-Selective Combination Cancer Therapy".

ACS Appl Mater Interfaces 2020 03 5;12(11):13584. Epub 2020 Mar 5.

Department of Chemistry, Kwangwoon University, 20 Gwangwoon-ro, Nowon-gu, Seoul 01897, Republic of Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c02360DOI Listing
March 2020

Environmentally Friendly Synthesis of Au-Te-Clustered Nanoworms via Galvanic Replacement for Wavelength-Selective Combination Cancer Therapy.

ACS Appl Mater Interfaces 2020 Feb 23;12(5):5511-5519. Epub 2020 Jan 23.

Department of Chemistry , Kwangwoon University , 20 Gwangwoon-ro , Nowon-gu, Seoul 01897 , Republic of Korea.

Au-Te-clustered nanoworms (AuTeNWs) were successfully synthesized under ambient conditions by spontaneous galvanic replacement using Te nanorods as a sacrificial nanotemplate. Along with the gradual replacement and on-surface crystalline Au cluster formation, Te nanotemplates were transformed into a serpentine nanoworm-like morphology. The present strategy was an environmentally friendly method that did not use surfactants to control the surface structure. The synthesized nanoworms exhibited excellent photothermal conversion, photocatalytic efficiencies, and high payloads for thiolated genes and cell-penetrating peptides. According to the visible and near-infrared wavelengths of light, the photodynamic and photothermal therapeutic pathways were dominantly acting, respectively. From this, wavelength-selective combination treatment with gene therapy was successfully accomplished. Taken together, excellent therapeutic effects for in vitro and in vivo mouse models against hepatitis C replicon human hepatocarcinoma were clearly identified by using the present AuTeNWs as a phototherapeutic nanocarrier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b19862DOI Listing
February 2020

Plant-Derived Purification, Chemical Synthesis, and In Vitro/In Vivo Evaluation of a Resveratrol Dimer, Viniferin, as an HCV Replication Inhibitor.

Viruses 2019 09 23;11(10). Epub 2019 Sep 23.

College of Pharmacy, Dongguk University, Goyang 10326, Korea.

Oligostilbenoid compounds, a group of resveratrol multimers, display several anti-microbial activities through the neutralization of cytotoxic oxidants, and by inhibiting essential host and viral enzymes. In our previous study, we identified a series of oligostilbenoid compounds as potent hepatitis C virus (HCV) replication inhibitors. In particular, vitisin B, a resveratrol tetramer, exhibited the most dramatic anti-HCV activity (EC = 6 nM and CC > 10 μM) via the disruption of the viral helicase NS3 (IC = 3 nM). However, its further development as an HCV drug candidate was halted due to its intrinsic drawbacks, such as poor stability, low water solubility, and restricted in vivo absorption. In order to overcome these limitations, we focused on (+)-ε-viniferin, a resveratrol dimer, as an alternative. We prepared three different versions of (+)-ε-viniferin, including one which was extracted from the grapevine root (EVF) and two which were chemically synthesized with either penta-acetylation (SVF-5Ac) or no acetylation (SVF) using a newly established synthesis method. We confirmed their anti-HCV replication activities and minimal cytotoxicity by using genotype 1b and 2a HCV replicon cells. Their anti-HCV replication action also translated into a significant reduction of viral protein expression. Anti-HCV NS3 helicase activity by EVF was also verified in vitro. Finally, we demonstrated that SVF has improved pharmacokinetic properties over vitisin B. Overall, the favorable antiviral and pharmacokinetic properties of these three versions of viniferin warrant their further study as members of a promising new class of anti-HCV therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v11100890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832221PMC
September 2019

Fucoidan-coated coral-like Pt nanoparticles for computed tomography-guided highly enhanced synergistic anticancer effect against drug-resistant breast cancer cells.

Nanoscale 2019 Aug;11(32):15173-15183

Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.

Chemotherapy, the most commonly applied cancer treatment, often causes unexpected failure due to multidrug resistance (MDR). To overcome MDR, we have designed a platform to realize a combinational synergistic effect of a natural bioactive product (fucoidan), anticancer small compound (doxorubicin), and photothermal nanocarrier (Pt nanoparticle) to treat drug-resistant breast cancer cells. Especially, fucoidan, a sulfated, polysaccharide-structured, therapeutic biopolymer, has been recently recognized as a potential anticancer compound; however, its cancer-inhibiting efficacy has been regarded as low owing to its insufficient level in serum following its conventional oral ingestion. To enhance its potency, fucoidan was applied as a biocompatible surfactant and surface-coating biopolymer in nanocarrier synthesis to manufacture coral-like, fucoidan-coated Pt nanoparticles with a rough surface morphology by a one-pot method. As a result, the biological-thermo-chemo trimodal combination treatment showed excellent therapeutic efficiency against the MDR breast cancer cell MCF-7 ADR both in vitro and in vivo, and the computed tomography contrast effect was also confirmed from the constituent element Pt. Beyond universal application in drug delivery and photothermal therapy, the present approach of applying a MDR modulating/anticancer natural product from nanoparticle synthesis to theranostics will contribute greatly to maximizing their potential through interdisciplinary convergence in the near future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9nr04495gDOI Listing
August 2019

Design rules for a tunable merged-tip microneedle.

Microsyst Nanoeng 2018 22;4:29. Epub 2018 Oct 22.

1School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, 08826 South Korea.

This publication proposes the use of an elasto-capillarity-driven self-assembly for fabricating a microscale merged-tip structure out of a variety of biocompatible UV-curable polymers for use as a microneedle platform. In addition, the novel merged-tip microstructure constitutes a new class of microneedles, which incorporates the convergence of biocompatible polymer micropillars, leading to the formation of a sharp tip and an open cavity capable of both liquid trapping and volume control. When combined with biocompatible photopolymer micropillar arrays fabricated with photolithography, elasto-capillarity-driven self-assembly provides a means for producing a complex microneedle-like structure without the use of micromolding or micromachining. This publication also explores and defines the design rules by which several fabrication aspects, such as micropillar dimensions, shapes, pattern array configurations, and materials, can be manipulated to produce a customizable microneedle array with controllable cavity volumes, fracture points, and merge profiles. In addition, the incorporation of a modular through-hole micropore membrane base was also investigated as a method for constitutive payload delivery and fluid-sampling functionalities. The flexibility and fabrication simplicity of the merged-tip microneedle platform holds promise in transdermal drug delivery applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41378-018-0028-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220166PMC
October 2018

Direct Monitoring of Cancer-Associated mRNAs in Living Cells to Evaluate the Therapeutic RNAi Efficiency Using Fluorescent Nanosensor.

ACS Sens 2019 05 24;4(5):1174-1179. Epub 2019 Apr 24.

Department of Chemistry , Seoul National University , Seoul , 08826 , Republic of Korea.

Cancer-associated mRNA (mRNA) is an important biomarker for early diagnosis, prognosis, and prediction of treatment responses. Despite recent developments in fluorescence live cell imaging, reliable detection and quantification of mRNA in living cells still remain challenging due to a complicated intracellular environment. Herein, we present a fluorescent nanosensor for live-cell monitoring of cancer-related mRNAs involved in the canonical Wnt/β-catenin signaling pathway. The nanosensor enables rapid and accurate assessment of gene downregulation efficiency in a dose- and time-dependent manner by measuring quantitative fluorescence signal corresponding to β-catenin or its target mRNA levels in living cells. It is expected that the fluorescent nanosensor will be applicable to high-throughput screening for the efficient drug discovery and insightful understanding of the molecular mechanisms of potential drug candidate for cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssensors.8b01498DOI Listing
May 2019

Hydrothermal Galvanic-Replacement-Tethered Synthesis of Ir-Ag-IrO Nanoplates for Computed Tomography-Guided Multiwavelength Potent Thermodynamic Cancer Therapy.

ACS Nano 2019 03 15;13(3):3434-3447. Epub 2019 Mar 15.

Department of Chemistry , Kwangwoon University , 20, Gwangwoon-ro , Nowon-gu, Seoul 01897 , Republic of Korea.

Beyond the synthesis of typical nanocrystals, various breakthrough approaches have been developed to provide more useful structural features and functionalities. Among them, galvanic replacement, a structural transformation reaction accompanied by constituent element substitution, has been applied to various areas. However, the innovative improvement for galvanic replacement needs to be considered because of the limitation of applicable element pairs to maintain structural stability. To expand the boundary of galvanic-replacement-mediated synthesis, we have become interested in the Group 9 metallic element Ir, which is considered a fascinating element in the field of catalysis, but whose size and shape regulation has been conventionally regarded as difficult. To overcome the current limitations, we developed a hydrothermal galvanic-replacement-tethered synthetic route to prepare Ir-Ag-IrO nanoplates (IrNPs) with a transverse length of tens of nanometers and a rough surface morphology. A very interesting photoreactivity was observed from the prepared IrNPs, with Ag and IrO coexisting partially, which showed photothermal conversion and photocatalytic activity at different ratios against extinction wavelengths of 473, 660, and 808 nm. The present IrNP platform showed excellent photothermal conversion efficiency under near-infrared laser irradiation at 808 nm and also represented an effective cancer treatment in vitro and in vivo through a synergistic effect with reactive oxygen species (ROS) generation. In addition, computed tomography (CT) imaging contrast effects from Ir and IrO composition were also clearly observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.8b09516DOI Listing
March 2019

A FRET assay for the quantitation of inhibitors of exonuclease EcoRV by using parchment paper inkjet-printed with graphene oxide and FAM-labelled DNA.

Mikrochim Acta 2019 03 4;186(4):211. Epub 2019 Mar 4.

College of Pharmacy, Seoul National University, Seoul, 08826, South Korea.

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 parchment paper. The ssDNA region binds to the surface of GO and anchors so that the fluorescence of FAM is quenched. The parchment paper strip is then incubated with a sample containing EcoRV which causes enzymatic hydrolysis, and dsDNA was separated from the GO. As a result, green fluorescence is generated at the reaction spot. Enzyme activity can be measured in the presence and absence of aurintricarboxy acid acting as an EcoRV inhibitor. This method excels by its need for 2-3 orders less reagents compared to the standard well plate assay. Thus, it is an efficient platform for GO-based screening of EcoRV enzyme inhibitors. Graphical abstract A graphene oxide (GO)-based endonuclease EcoRV inhibition FRET assay using inkjet printing was developed. Printing of GO along with assay reagents has a beneficial effect on the enzymatic reaction on paper. This method was successfully applied to evaluate EcoRV inhibitor activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00604-019-3317-9DOI Listing
March 2019

Reliable autapse formation using the single-cell patterning method.

Biofabrication 2018 11 13;11(1):015008. Epub 2018 Nov 13.

Division of WCU (World Class University) Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea.

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 autapses for electrophysiological analysis using multi-electrode arrays (MEA). The pattern arrays were formed by selective patterning of poly-L-lysine and various cell repellent materials. We tested the efficiency of single neuron pattern formed according to materials and pattern dimensions. Autapse formation was verified by immunostaining synaptic markers and physiological measurements via recordings from MEA. The results demonstrated that our multiscale patterning method increased the number of autapses consisting of a single neuron, which matured to connect onto themselves. The proposed patterning method (4.06 ± 0.33 isolated single-cells mm) is at least twelve times more efficient and productive than the spray method (0.31 ± 0.10 isolated single-cells mm). The spontaneous activity of a single neuron on the patterned MEA occured after 11 d in vitro. The single neuron activity consisted of bursts followed by spike trains (the burst rate was 2.56 min). This indicates that our method could be used for electrophysiological analysis, including MEA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1758-5090/aaeb66DOI Listing
November 2018

Synthesis of porous Pd nanoparticles by therapeutic chaga extract for highly efficient tri-modal cancer treatment.

Nanoscale 2018 Nov;10(42):19810-19817

Department of Chemistry, Kwangwoon University, 20, Gwangwoon-ro, Nowon-gu, Seoul 01897, Republic of Korea.

Porous palladium nanoparticles were designed and synthesized to maximize the pharmacological activity of the chaga mushroom (Inonotus obliquus) extract, which has anticancer and antibacterial activities. In the present study, we synthesized anisotropic porous Pd nanostructures with ultraviolet-visible-near infrared whole wavelength region absorption using chaga extract concentration-dependent reductant-mediated synthesis. The porous Pd nanoparticles exhibited a surface chaga extract-derived anticancer effect, controlled delivery of doxorubicin through electrostatic interaction, and a photothermal conversion effect under 808 nm laser irradiation. The combined application of the three cancer treatment approaches clearly demonstrated the feasibility of synergistic tri-modal therapy. The present platform using Pd, which is a key constituent element of nanocatalysts but is not commonly used in biological applications, suggests numerous applications utilizing Pd nanostructures, as well as the potential development of new cancer therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8nr07172aDOI Listing
November 2018

Synthesis of biologically-active reduced graphene oxide by using fucoidan as a multifunctional agent for combination cancer therapy.

Nanotechnology 2018 Nov 7;29(47):475604. Epub 2018 Sep 7.

Department of Chemistry, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

A therapeutic reduced graphene oxide (RGO) is synthesized by using fucoidan (Fu) as the reducing and surface functionalizing agent. The synthesized Fu-RGO exhibits promising characteristics for therapeutic applications such as high dispersity in aqueous media, biocompatibility, selective cytotoxicity to cancer cells, high loading capacity of the anticancer drug, and photothermal conversion effect. Therefore, Fu-GO is successfully harnessed as a combinatorial cancer treatment platform through bio-functional (Fu), chemo (doxorubicin (Dox)) and photothermal (RGO with near-infrared irradiation) modalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6528/aadfa5DOI Listing
November 2018

High-throughput chemical screening to discover new modulators of microRNA expression in living cells by using graphene-based biosensor.

Sci Rep 2018 07 30;8(1):11413. Epub 2018 Jul 30.

Department of Chemistry, Seoul National University, Seoul, 08826, Republic of Korea.

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 to identify small molecules that modulate miRNA expression in living cells. The screen enables simultaneous monitoring of the phenotypic cellular changes associated with the miRNA expression by measuring quantitative fluorescent signals corresponding to target miRNA level in living cells based on a novel biosensor composed of peptide nucleic acid and nano-sized graphene oxide. In this study, the biosensor based cellular screening of 967 compounds (including FDA-approved drugs, enzyme inhibitors, agonists, and antagonists) in cells identified four different classes of small molecules consisting of (i) 70 compounds that suppress both miRNA-21 (miR-21) expression and cell proliferation, (ii) 65 compounds that enhance miR-21 expression and reduce cell proliferation, (iii) 2 compounds that suppress miR-21 expression and increase cell proliferation, and (iv) 21 compounds that enhance both miR-21 expression and cell proliferation. We further investigated the hit compounds to correlate cell morphology changes and cell migration ability with decreased expression of miR-21.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-29633-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065314PMC
July 2018

Morphology-Controlled Synthesis of Rhodium Nanoparticles for Cancer Phototherapy.

ACS Nano 2018 07 22;12(7):6997-7008. Epub 2018 Jun 22.

Department of Chemistry , Kwangwoon University , 20, Gwangwoon-ro , Nowon-gu, Seoul 01897 , Republic of Korea.

Rhodium nanoparticles are promising transition metal nanocatalysts for electrochemical and synthetic organic chemistry applications. However, notwithstanding their potential, to date, Rh nanoparticles have not been utilized for biological applications; there has been no cytotoxicity study of Rh reported in the literature. In this regard, the absence of a facile and controllable synthetic strategy of Rh nanostructures with various sizes and morphologies might be responsible for the lack of progress in this field. Herein, we have developed a synthetic strategy for Rh nanostructures with controllable morphology through an inverse-directional galvanic replacement reaction. Three types of Rh-based nanostructures-nanoshells, nanoframes, and porous nanoplates-were successfully synthesized. A plausible synthetic mechanism based on thermodynamic considerations has also been proposed. The cytotoxicity, surface functionalization, and photothermal therapeutic effect of manufactured Rh nanostructures were systematically investigated to reveal their potential for in vitro and in vivo biological applications. Considering the comparable behavior of porous Rh nanoplates to that of gold nanostructures that are widely used in nanomedicine, the present study introduces Rh-based nanostructures into the field of biological research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.8b02698DOI Listing
July 2018

Investigation on vascular cytotoxicity and extravascular transport of cationic polymer nanoparticles using perfusable 3D microvessel model.

Acta Biomater 2018 08 26;76:154-163. Epub 2018 May 26.

School of Mechanical and Aerospace Engineering, Seoul National University, Seoul 08826, South Korea. Electronic address:

Vascular networks are the first sites exposed to cationic polymer nanoparticles (NPs) administered intravenously, and thus function as a barrier for NPs reaching the target organ. While cationic polymer NPs have been intensively studied as non-viral delivery systems, their biological effects in human microvessels have been poorly investigated due to a lack of appropriate in vitro systems. Here, we employed a three-dimensional microvessel on a chip, which accurately models in vivo conditions. An open and perfused microvessel surrounded by pericytes was shown to reproduce the important features of living vasculature, including barrier function and biomarkers. Using this microvessel chip, we observed contraction of the microvascular lumen induced by perfused polyethylenimine (PEI)/DNA NPs. We demonstrated that the oxidative stress present when microvessels were exposed to PEI NPs led to rearrangement of microtubules resulting in microvessel contraction. Furthermore, the transcytotic behavior of PEI NPs was analyzed in the microvessel by monitoring the escape of PEI NPs from the microvascular lumen into the perivascular region, which was not possible in two-dimensional culture systems. With our new understanding of the different behaviors of cationic polymer NPs depending on their transcytotic route, we suggest that caveolae-mediated transcytosis is a powerful route for efficient extravascular transport.

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 due to lack of appropriate in vitro systems. Here, we microengineered an open and perfused 3D pericyte incorporated microvessel model which possesses same morphological characteristic of in vivo. Using the microengineered model, this study represents the first report of transcytotic behavior of NPs in 3D microvessel, and its effect on extravasation efficiency. Our study lays the groundwork for the integration of innovative technologies to examine blood vessel-nanoparticle interaction, which a critical but ill-defined phenomenon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2018.05.041DOI Listing
August 2018

Revisiting of Pd Nanoparticles in Cancer Treatment: All-Round Excellence of Porous Pd Nanoplates in Gene-Thermo Combinational Therapy.

ACS Appl Mater Interfaces 2018 Apr 11;10(16):13819-13828. Epub 2018 Apr 11.

Department of Chemistry , Kwangwoon University , 20, Gwangwoon-ro , Nowon-gu, Seoul 01897 , Republic of Korea.

Gold nanomaterials are commonly used in biomedical applications owing to their excellent biocompatibility and unique physicochemical and optical properties, whereas Pd nanomaterials are mainly used as catalysts. Here, we re-examined the possible applications of Pd nanomaterials. Reducing agent-assisted excessive galvanic replacement-mediated porous Au nanoplates, porous Pt nanoplates, and porous Pd nanoplate synthesis enabled us to compare the properties and efficiency of nanoplates composed of three metal elements (Au, Pt, and Pd). According to our analytical results, porous Pd nanoplates exhibited exceptional all-round excellence in photothermal conversion, therapeutic gene loading/releasing, cytotoxicity, and in vitro combination cancer treatment. We believe that this discovery broadens the potential applications of metal nanomaterials, with an emphasis on more efficient biomedical applications in limited conventional fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.8b01000DOI Listing
April 2018
-->