Publications by authors named "Kyung Soo Park"

69 Publications

Population Pharmacokinetics of Primaquine in the Korean Population.

Pharmaceutics 2021 May 3;13(5). Epub 2021 May 3.

Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Korea.

While primaquine has long been used for malaria treatment, treatment failure is common. This study aims to develop a population pharmacokinetic model of primaquine and its metabolite, carboxyprimaquine, and examine factors influencing pharmacokinetic variability. The data was obtained from a clinical study in 24 Korean subjects randomly assigned to normal and obese groups. The participants received primaquine 15 mg daily for 4 days and blood samples were collected at day 4. Pharmacokinetic modeling was performed with NONMEM and using simulations; the influences of doses and covariates on drug exposure were examined. A minimal physiology-based pharmacokinetic model connected with a liver compartment comprehensively described the data, with CYP450 mediated clearance being positively correlated with the body weight and CYP2D6 activity score ( < 0.05). In the simulation, while the weight-normalized area under drug concentration for primaquine in the obese group decreased by 29% at the current recommended dose of 15 mg, it became similar to the normal weight group at a weight-normalized dose of 3.5 mg/kg. This study has demonstrated that the body weight and CYP2D6 activity score significantly influence the pharmacokinetics of primaquine. The developed model is expected to be used as a basis for optimal malaria treatment in Korean patients.
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http://dx.doi.org/10.3390/pharmaceutics13050652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147617PMC
May 2021

Personalized combination nano-immunotherapy for robust induction and tumor infiltration of CD8 T cells.

Biomaterials 2021 Jul 27;274:120844. Epub 2021 Apr 27.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address:

Identification of tumor-specific mutations, called neoantigens, offers new exciting opportunities for personalized cancer immunotherapy. However, it remains challenging to achieve robust induction of neoantigen-specific T cells and drive their infiltration into the tumor microenvironment (TME). Here, we have developed a novel polyethyleneimine (PEI)-based personalized vaccine platform carrying neoantigen peptides and CpG adjuvants in a compact nanoparticle (NP) for their spatio-temporally concerted delivery. The NP vaccine significantly enhanced activation and antigen cross-presentation of dendritic cells, resulting in strong priming of neoantigen-specific CD8 T cells with the frequency in the systemic circulation reaching as high as 23 ± 7% after a single subcutaneous administration. However, activated CD8 T cells in circulation exhibited limited tumor infiltration, leading to poor anti-tumor efficacy. Notably, local administration of stimulator of interferon genes (STING) agonist promoted tumor infiltration of vaccine-primed CD8 T cells, thereby overcoming one of the major challenges in achieving strong anti-tumor efficacy with cancer vaccination. The NP vaccination combined with STING agonist therapy eliminated tumors in murine models of MC-38 colon carcinoma and B16F10 melanoma and established long-term immunological memory. Our approach provides a novel therapeutic strategy based on combination nano-immunotherapy for personalized cancer immunotherapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184601PMC
July 2021

Modularly Programmable Nanoparticle Vaccine Based on Polyethyleneimine for Personalized Cancer Immunotherapy.

Adv Sci (Weinh) 2021 Mar 6;8(5):2002577. Epub 2021 Jan 6.

Department of Pharmaceutical Sciences Department of Biomedical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.

Nanoparticles (NPs) can serve as a promising vaccine delivery platform for improving pharmacological property and codelivery of antigens and adjuvants. However, NP-based vaccines are generally associated with complex synthesis and postmodification procedures, which pose technical and manufacturing challenges for tailor-made vaccine production. Here, modularly programmed, polyethyleneimine (PEI)-based NP vaccines are reported for simple production of personalized cancer vaccines. Briefly, PEI is conjugated with neoantigens by facile coupling chemistry, followed by electrostatic assembly with CpG adjuvants, leading to the self-assembly of nontoxic, sub-50 nm PEI NPs. Importantly, PEI NPs promote activation and antigen cross-presentation of antigen-presenting cells and cross-priming of neoantigen-specific CD8 T cells. Surprisingly, after only a single intratumoral injection, PEI NPs with optimal PEGylation elicit as high as ≈30% neoantigen-specific CD8 T cell response in the systemic circulation and sustain elevated CD8 T cell response over 3 weeks. PEI-based nanovaccines exert potent antitumor efficacy against pre-established local tumors as well as highly aggressive metastatic tumors. PEI engineering for modular incorporation of neoantigens and adjuvants offers a promising strategy for rapid and facile production of personalized cancer vaccines.
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http://dx.doi.org/10.1002/advs.202002577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927624PMC
March 2021

Lipid-based vaccine nanoparticles for induction of humoral immune responses against HIV-1 and SARS-CoV-2.

J Control Release 2021 02 20;330:529-539. Epub 2020 Dec 20.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

The current health crisis of corona virus disease 2019 (COVID-19) highlights the urgent need for vaccine systems that can generate potent and protective immune responses. Protein vaccines are safe, but conventional approaches for protein-based vaccines often fail to elicit potent and long-lasting immune responses. Nanoparticle vaccines designed to co-deliver protein antigens and adjuvants can promote their delivery to antigen-presenting cells and improve immunogenicity. However, it remains challenging to develop vaccine nanoparticles that can preserve and present conformational epitopes of protein antigens for induction of neutralizing antibody responses. Here, we have designed a new lipid-based nanoparticle vaccine platform (NVP) that presents viral proteins (HIV-1 and SARS-CoV-2 antigens) in a conformational manner for induction of antigen-specific antibody responses. We show that NVP was readily taken up by dendritic cells (DCs) and promoted DC maturation and antigen presentation. NVP loaded with BG505.SOSIP.664 (SOSIP) or SARS-CoV-2 receptor-binding domain (RBD) was readily recognized by neutralizing antibodies, indicating the conformational display of antigens on the surfaces of NVP. Rabbits immunized with SOSIP-NVP elicited strong neutralizing antibody responses against HIV-1. Furthermore, mice immunized with RBD-NVP induced robust and long-lasting antibody responses against RBD from SARS-CoV-2. These results suggest that NVP is a promising platform technology for vaccination against infectious pathogens.
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http://dx.doi.org/10.1016/j.jconrel.2020.12.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749995PMC
February 2021

Non-viral COVID-19 vaccine delivery systems.

Adv Drug Deliv Rev 2021 02 17;169:137-151. Epub 2020 Dec 17.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

The novel corona virus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the globe at a formidable speed, causing tens of millions of cases and more than one million deaths in less than a year of its report in December 2019. Since then, companies and research institutions have raced to develop SARS-CoV-2 vaccines, ranging from conventional viral and protein-based vaccines to those that are more cutting edge, including DNA- and mRNA-based vaccines. Each vaccine exhibits a different potency and duration of efficacy, as determined by the antigen design, adjuvant molecules, vaccine delivery platforms, and immunization method. In this review, we will introduce a few of the leading non-viral vaccines that are under clinical stage development and discuss delivery strategies to improve vaccine efficacy, duration of protection, safety, and mass vaccination.
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http://dx.doi.org/10.1016/j.addr.2020.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744276PMC
February 2021

Efficient Lymph Node-Targeted Delivery of Personalized Cancer Vaccines with Reactive Oxygen Species-Inducing Reduced Graphene Oxide Nanosheets.

ACS Nano 2020 10 15;14(10):13268-13278. Epub 2020 Sep 15.

Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.

Therapeutic cancer vaccines require robust cellular immunity for the efficient killing of tumor cells, and recent advances in neoantigen discovery may provide safe and promising targets for cancer vaccines. However, elicitation of T cells with strong antitumor efficacy requires intricate multistep processes that have been difficult to attain with traditional vaccination approaches. Here, a multifunctional nanovaccine platform has been developed for direct delivery of neoantigens and adjuvants to lymph nodes (LNs) and highly efficient induction of neoantigen-specific T cell responses. A PEGylated reduced graphene oxide nanosheet (RGO-PEG, 20-30 nm in diameter) is a highly modular and biodegradable platform for facile preparation of neoantigen vaccines within 2 h. RGO-PEG exhibits rapid, efficient (15-20% ID/g), and sustained (up to 72 h) accumulation in LNs, achieving >100-fold improvement in LN-targeted delivery, compared with soluble vaccines. Moreover, RGO-PEG induces intracellular reactive oxygen species in dendritic cells, guiding antigen processing and presentation to T cells. Importantly, a single injection of RGO-PEG vaccine elicits potent neoantigen-specific T cell responses lasting up to 30 days and eradicates established MC-38 colon carcinoma. Further combination with anti-PD-1 therapy achieved great therapeutic improvements against B16F10 melanoma. RGO-PEG may serve a powerful delivery platform for personalized cancer vaccination.
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http://dx.doi.org/10.1021/acsnano.0c05062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606610PMC
October 2020

Alveolar macrophage secretion of vesicular SOCS3 represents a platform for lung cancer therapeutics.

JCI Insight 2019 10 17;4(20). Epub 2019 Oct 17.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Lung cancer remains the leading cause of cancer-related death in the United States. Although the alveolar macrophage (AM) comprises the major resident immune cell in the lung, few studies have investigated its role in lung cancer development. We recently discovered a potentially novel mechanism wherein AMs regulate STAT-induced inflammatory responses in neighboring epithelial cells (ECs) via secretion and delivery of suppressors of cytokine signaling 3 (SOCS3) within extracellular vesicles (EVs). Here, we explored the impact of SOCS3 transfer on EC tumorigenesis and the integrity of AM SOCS3 secretion during development of lung cancer. AM-derived EVs containing SOCS3 inhibited STAT3 activation as well as proliferation and survival of lung adenocarcinoma cells. Levels of secreted SOCS3 were diminished in lungs of patients with non-small cell lung cancer and in a mouse model of lung cancer, and the impaired ability of murine AMs to secrete SOCS3 within EVs preceded the development of lung tumors. Loss of this homeostatic brake on tumorigenesis prompted our effort to "rescue" it. Provision of recombinant SOCS3 loaded within synthetic liposomes inhibited proliferation and survival of lung adenocarcinoma cells in vitro as well as malignant transformation of normal ECs. Intratumoral injection of SOCS3 liposomes attenuated tumor growth in a lung cancer xenograft model. This work identifies AM-derived vesicular SOCS3 as an endogenous antitumor mechanism that is disrupted within the tumor microenvironment and whose rescue by synthetic liposomes can be leveraged as a potential therapeutic strategy for lung cancer.
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http://dx.doi.org/10.1172/jci.insight.131340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824301PMC
October 2019

Engineering patient-specific cancer immunotherapies.

Nat Biomed Eng 2019 10 12;3(10):768-782. Epub 2019 Aug 12.

Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.

Research into the immunological processes implicated in cancer has yielded a basis for the range of immunotherapies that are now considered the fourth pillar of cancer treatment (alongside surgery, radiotherapy and chemotherapy). For some aggressive cancers, such as advanced non-small-cell lung carcinoma, combination immunotherapies have resulted in unprecedented treatment efficacy for responding patients, and have become frontline therapies. Individualized immunotherapy, enabled by the identification of patient-specific mutations, neoantigens and biomarkers, and facilitated by advances in genomics and proteomics, promises to broaden the responder patient population. In this Perspective, we give an overview of immunotherapies leveraging engineering approaches, including the design of biomaterials, delivery strategies and nanotechnology solutions, for the realization of individualized cancer treatments such as nanoparticle vaccines customized with neoantigens, cell therapies based on patient-derived dendritic cells and T cells, and combinations of theranostic strategies. Developments in precision cancer immunotherapy will increasingly rely on the adoption of engineering principles.
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http://dx.doi.org/10.1038/s41551-019-0436-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783331PMC
October 2019

Bioinspired nucleic acid structures for immune modulation.

Biomaterials 2019 10 19;217:119287. Epub 2019 Jun 19.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address:

Nucleic acids have both extensive physiological function and structural potential, rendering them quintessential engineering biomaterials. As carriers of precisely-tunable genetic information, both DNA and RNA can be synthetically generated to form a myriad of structures and to transmit specific genetic code. Importantly, recent studies have shown that DNA and RNA, both in their native and engineered forms, can function as potent regulators of innate immunity, capable of initiating and modulating immune responses. In this review, we highlight recent advances in biomaterials inspired by the various interactions of nucleic acids and the immune system. We discuss key advances in self-assembled structures based on exogenous nucleic acids and engineering approaches to apply endogenous nucleic acids as found in immunogenic cell death and extracellular traps. In addition, we discuss new strategies to control dinucleotide signaling and provide recent examples of biomaterials designed for cancer immunotherapy with STING agonists.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635102PMC
October 2019

Synthesis of cosmetic grade TiO-SiO core-shell powder from mechanically milled TiO nanopowder for commercial mass production.

Mater Sci Eng C Mater Biol Appl 2019 Feb 3;95:95-103. Epub 2018 Oct 3.

Advanced Materials & Processing Center, Institute for Advanced Engineering (IAE), Yongin, Republic of Korea. Electronic address:

TiO nanoparticles as an active sunscreen ingredient generate reactive oxygen species (ROS) upon UVA irradiation which is cytotoxic, genotoxic and potential to damage the DNA. The health concern and potential risks from TiO can be mitigated by shielding the particles through the suitable coating. Considering the advantages of SiO, SiO coated TiO nanoparticles can be a potential material which can replace TiO for thickening, whitening, lubricating, and sunscreen ingredient in cosmetics. This article reports the synthesis of cosmetic grade TiO-SiO core-shell nanopowder from mechanically milled TiO nanopowder for commercial mass production. From commercial TiO nanopowder was fabricated through size reduction by nanoset milling. Followed by the fabricated TiO nanopowder coated with SiO through sol-gel technique. A suitable optimum condition was explored for cosmetic grade TiO-SiO core-shell nanopowder. Various physical properties and optical properties were analyzed. Synthesized of cosmetic grade TiO-SiO core-shell nanopowder found to be at 100 nm size, with a homogeneous SiO coating having UVA protection factor 39 and sun protection factor (SPF) is 42. From the size, safety, and SPF perspective it can be an excellent cosmetic grade powder and from process simplicity perspective it can be commercially viable.
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http://dx.doi.org/10.1016/j.msec.2018.10.005DOI Listing
February 2019

Aqueous Phase Synthesis of 5-Hydroxymethylfurfural from Glucose over Large Pore Mesoporous Zirconium Phosphates: Effect of Calcination Temperature.

ACS Omega 2018 Jan 22;3(1):808-820. Epub 2018 Jan 22.

School of Chemical Engineering, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.

For a solid acid-catalyzed dehydration of biomass-derived carbohydrates into useful furan derivatives, a suitable porous solid acid catalyst having an optimum acidic density and its strength is required to avoid cascade reactions in biomass conversion processes. A large-pore mesoporous zirconium phosphate (-ZrP) was prepared hydrothermally using P123 as a template in water solvent, which resulted in a higher pore diameter (>9 nm) having wormhole-like pore structures with balanced Lewis (L) to Brönsted (B) acid sites. The effects of calcination temperature (500-800 °C) on the textural, acidic/basic, and structural properties of the -ZrP with its catalytic performance for glucose dehydration to 5-hydroxymethylfurfural (HMF) were investigated in a pure water media as a green and sustainable alternative solvent. The larger number of L and B acid sites and basic sites with their appropriate strengths were clearly related with a better catalytic performance in terms of glucose conversion and HMF yield. The strong L acid and basic sites in the -ZrP efficiently promoted the glucose isomerization to fructose, which dehydrated exclusively on the weak B acid sites resulting in a maximum conversion of glucose (83.8%) and HMF yield (46.6%). The adjusted acidic and basic sites with large mesopore sizes make the -ZrP yield a higher reaction rate (2.78 mmol g h) and turnover frequency (11.68/h) for conversion of glucose to HMF, which showed higher catalytic activity than those of a small-pore -ZrP and other mesoporous heterogeneous and homogeneous acid catalysts.
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http://dx.doi.org/10.1021/acsomega.7b01357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641390PMC
January 2018

Use of a botulinum toxin A in dentistry and oral and maxillofacial surgery.

J Dent Anesth Pain Med 2016 Sep 30;16(3):151-157. Epub 2016 Sep 30.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Korea.

Botulinum toxin (BT) was the first toxin to be used in the history of human medicine. Among the eight known serotypes of this toxin, those currently used in medicine are types A and B. This review article mainly discusses BT type A (BTA) because it is usually used in dentistry including dental anesthesiology and oral and maxillofacial surgery. BTA has been used mainly in the treatment of temporomandibular joint disorder (TMD) and hypertrophy and hyperactivity of the masticatory muscles, along with being a therapeutic option to relieve pain and help in functional recovery from dental and oral and maxillofacial surgery. However, it is currently used broadly for cosmetic purposes such as reducing facial wrinkles and asymmetry. Although the therapeutic effect of BTA is temporary and relatively safe, it is essential to have knowledge about related anatomy, as well as the systemic and local adverse effects of medications that are applied to the face.
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http://dx.doi.org/10.17245/jdapm.2016.16.3.151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586551PMC
September 2016

Phototactic guidance of a tissue-engineered soft-robotic ray.

Science 2016 Jul;353(6295):158-62

Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. Sogang-Harvard Research Center for Disease Biophysics, Sogang University, Seoul 121-742, Korea.

Inspired by the relatively simple morphological blueprint provided by batoid fish such as stingrays and skates, we created a biohybrid system that enables an artificial animal--a tissue-engineered ray--to swim and phototactically follow a light cue. By patterning dissociated rat cardiomyocytes on an elastomeric body enclosing a microfabricated gold skeleton, we replicated fish morphology at 1/10 scale and captured basic fin deflection patterns of batoid fish. Optogenetics allows for phototactic guidance, steering, and turning maneuvers. Optical stimulation induced sequential muscle activation via serpentine-patterned muscle circuits, leading to coordinated undulatory swimming. The speed and direction of the ray was controlled by modulating light frequency and by independently eliciting right and left fins, allowing the biohybrid machine to maneuver through an obstacle course.
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http://dx.doi.org/10.1126/science.aaf4292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526330PMC
July 2016

Multiplexed labeling system for high-throughput cell sorting.

Anal Biochem 2016 09 12;508:124-8. Epub 2016 May 12.

School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, South Korea; SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 440-746, South Korea. Electronic address:

Flow cytometry and fluorescence activated cell sorting techniques were designed to realize configurable classification and separation of target cells. A number of cell phenotypes with different functionalities have recently been revealed. Before simultaneous selective capture of cells, it is desirable to label different samples with the corresponding dyes in a multiplexing manner to allow for a single analysis. However, few methods to obtain multiple fluorescent colors for various cell types have been developed. Even when restricted laser sources are employed, a small number of color codes can be expressed simultaneously. In this study, we demonstrate the ability to manifest DNA nanostructure-based multifluorescent colors formed by a complex of dyes. Highly precise self-assembly of fluorescent dye-conjugated oligonucleotides gives anisotropic DNA nanostructures, Y- and tree-shaped DNA (Y-DNA and T-DNA, respectively), which may be used as platforms for fluorescent codes. As a proof of concept, we have demonstrated seven different fluorescent codes with only two different fluorescent dyes using T-DNA. This method provides maximum efficiency for current flow cytometry. We are confident that this system will provide highly efficient multiplexed fluorescent detection for bioanalysis compared with one-to-one fluorescent correspondence for specific marker detection.
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http://dx.doi.org/10.1016/j.ab.2016.05.004DOI Listing
September 2016

Arsenic levels in the groundwater of Korea and the urinary excretion among contaminated area.

J Expo Sci Environ Epidemiol 2016 09 6;26(5):458-63. Epub 2016 Apr 6.

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

Drinking water is a main source of human exposure to arsenic. Hence, the determination of arsenic in groundwater is essential to assess its impact on public health. Here, we report arsenic levels in the groundwater of 722 sites covering all six major provinces of Korea. Water was sampled in two occasions (summer, 722 sites and winter, 636 sites) and the arsenic levels were measured with highly sensitive inductively coupled plasma-mass spectrometry method (limit of detection, 0.1 μg/l) to encompass the current drinking water standard (<10 μg/l). Seasonal variation was negligible, but the geographical difference was prominent. Total arsenic in groundwater ranged from 0.1 to 48.4 μg/l. A 88.0-89.0% of sites were <2.0 μg/l and the remaining ones generally did not exceed 10 μg/l (6.4-7.0%, 2.0-4.9 μg/l; 2.4-3.0%, 5.0-9.9 μg/l). However, some areas (1.0-9.2%) exhibited >10 μg/l. Notably, urinary arsenic excretion of people around these regions was markedly higher compared with non-contaminated areas (<5 μg/l) (79.7±5.2 μg/g (N=122) vs 68.4±5.4 μg/g (N=65) creatinine, P=0.052). All stratified analysis also revealed higher urinary excretion, where a statistically significant difference was noted for non-smokers (85.9±12.7 vs 54.0±6.3, P=0.030), suggesting that arsenic-contaminated groundwater may contribute to its systemic exposure.
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http://dx.doi.org/10.1038/jes.2016.16DOI Listing
September 2016

A Fluorescent Tile DNA Diagnocode System for In Situ Rapid and Selective Diagnosis of Cytosolic RNA Cancer Markers.

Sci Rep 2015 Dec 18;5:18497. Epub 2015 Dec 18.

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea.

Accurate cancer diagnosis often requires extraction and purification of genetic materials from cells, and sophisticated instrumentations that follow. Otherwise in order to directly treat the diagnostic materials to cells, multiple steps to optimize dose concentration and treatment time are necessary due to diversity in cellular behaviors. These processes may offer high precision but hinder fast analysis of cancer, especially in clinical situations that need rapid detection and characterization of cancer. Here we present a novel fluorescent tile DNA nanostructure delivered to cancer cytosol by employing nanoparticle technology. Its structural anisotropicity offers easy manipulation for multifunctionalities, enabling the novel DNA nanostructure to detect intracellular cancer RNA markers with high specificity within 30 minutes post treatment, while the nanoparticle property bypasses the requirement of treatment optimization, effectively reducing the complexity of applying the system for cancer diagnosis. Altogether, the system offers a precise and rapid detection of cancer, suggesting the future use in the clinical fields.
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http://dx.doi.org/10.1038/srep18497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683441PMC
December 2015

Enzyme-guided DNA Sewing Architecture.

Sci Rep 2015 Dec 4;5:17722. Epub 2015 Dec 4.

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, South Korea.

With the advent of nanotechnology, a variety of nanoarchitectures with varied physicochemical properties have been designed. Owing to the unique characteristics, DNAs have been used as a functional building block for novel nanoarchitecture. In particular, a self-assembly of long DNA molecules via a piece DNA staple has been utilized to attain such constructs. However, it needs many talented prerequisites (e.g., complicated computer program) with fewer yields of products. In addition, it has many limitations to overcome: for instance, (i) thermal instability under moderate environments and (ii) restraint in size caused by the restricted length of scaffold strands. Alternatively, the enzymatic sewing linkage of short DNA blocks is simply designed into long DNA assemblies but it is more error-prone due to the undeveloped sequence data. Here, we present, for the first time, a comprehensive study for directly combining DNA structures into higher DNA sewing constructs through the 5'-end cohesive ligation of T4 enzyme. Inspired by these achievements, the synthesized DNA nanomaterials were also utilized for effective detection and real-time diagnosis of cancer-specific and cytosolic RNA markers. This generalized protocol for generic DNA sewing is expected to be useful in several DNA nanotechnology as well as any nucleic acid-related fields.
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http://dx.doi.org/10.1038/srep17722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669507PMC
December 2015

Electrochemical Performances of Li2MnSiO4 Cathodes Synthesized by Mechanical Alloying Process.

J Nanosci Nanotechnol 2015 Mar;15(3):2418-21

We report the fabrication and electrochemical properties of Li2MnSiO4 powders produced by various solid-state reactions, such as ball-, attrition-, and bead-milling. Li2MnSiO4 powders prepared by bead-milling had the smallest particle sizes (~100 nm) and the largest amount of surface carbon (~20 wt%), which were produced by adding sucrose during milling process. The surface carbon layer can improve electronic/ionic conductivity of Li2MnSiO4 as cathode material for lithium ion battery. As expected, the bead-milled Li2MnSiO4 powder electrode showed the best electrochemical performance of the electrode materials obtained by the various solid-state reactions. This is attributed to the small particle size and facile electronic transport through the conductive carbon layer on each Li2MnSiO4 particle.
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http://dx.doi.org/10.1166/jnn.2015.10251DOI Listing
March 2015

Recycling of waste automotive laminated glass and valorization of polyvinyl butyral through mechanochemical separation.

Environ Res 2015 Oct;142:615-23

Institute for Advanced Engineering (IAE), Advanced Materials & Processing Center, Yongin-Si 449-863, Republic of Korea. Electronic address:

Due to strong binding, optical clarity, adhesion to many surfaces, toughness and flexibility polyvinyl butyral (PVB) resin films are commonly used in the automotive and architectural application as a protective interlayer in the laminated glass. Worldwide million tons of PVB waste generated from end-of-life automotive associated with various environmental issues. Stringent environmental directive, higher land cost eliminates land filling option, needs a study, we have developed a mechanochemical separation process to separate PVB resins from glass and characterized the separated PVB through various techniques, i.e., scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Commercial nonionic surfactants D201 used for the mechanochemical separation purpose. Through parameter optimization following conditions are considered to be the optimum condition; 30v ol% D201, stirring speed of 400 rpm, 35 °C temperature, operation time 1h, and dilute D201 volume to waste automotive laminated glass weight ratio of ≈25. The technology developed in our laboratory is sustainable, environmentally friendly, techno-economical feasible process, capable of mass production (recycling).
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http://dx.doi.org/10.1016/j.envres.2015.08.017DOI Listing
October 2015

mRNA-Producing Pseudo-nucleus System.

Small 2015 Nov 27;11(41):5515-9. Epub 2015 Aug 27.

School of Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.

A pseudo-eukaryotic nucleus (PEN) system consisting of a gene-containing DNA hydrogel encapsulated in a liposome is fabricated. Owing to the structural characteristics of gene-containing DNA hydrogel, mRNA transcription efficiency is promoted 2.57-fold. Through the use of PEN as a platform for mRNA delivery to the cytosol, prolonged protein translation is achieved.
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http://dx.doi.org/10.1002/smll.201501334DOI Listing
November 2015

Valorization of GaN based metal-organic chemical vapor deposition dust a semiconductor power device industry waste through mechanochemical oxidation and leaching: A sustainable green process.

Environ Res 2015 Jul 19;140:704-13. Epub 2015 Jun 19.

Department of Energy Engineering, Dankook University, Cheonan 330-714, Republic of Korea.

Dust generated during metal organic vapor deposition (MOCVD) process of GaN based semiconductor power device industry contains significant amounts of gallium and indium. These semiconductor power device industry wastes contain gallium as GaN and Ga0.97N0.9O0.09 is a concern for the environment which can add value through recycling. In the present study, this waste is recycled through mechanochemical oxidation and leaching. For quantitative recovery of gallium, two different mechanochemical oxidation leaching process flow sheets are proposed. In one process, first the Ga0.97N0.9O0.09 of the MOCVD dust is leached at the optimum condition. Subsequently, the leach residue is mechanochemically treated, followed by oxidative annealing and finally re-leached. In the second process, the MOCVD waste dust is mechanochemically treated, followed by oxidative annealing and finally leached. Both of these treatment processes are competitive with each other, appropriate for gallium leaching and treatment of the waste MOCVD dust. Without mechanochemical oxidation, 40.11 and 1.86 w/w% of gallium and Indium are leached using 4M HCl, 100°C and pulp density of 100 kg/m(3,) respectively. After mechanochemical oxidation, both these processes achieved 90 w/w% of gallium and 1.86 w/w% of indium leaching at their optimum condition.
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http://dx.doi.org/10.1016/j.envres.2015.06.003DOI Listing
July 2015

A novel multigene cloning method for the production of a motile ATPase.

J Biotechnol 2015 Aug 5;207:1-7. Epub 2015 May 5.

School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, South Korea; SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 440-746, South Korea. Electronic address:

With the advent of nanotechnology, new functional modules (e.g., nanomotors, nanoprobes) have become essential in several medical fields. Generally, mechanical modulators systems are the principal components of most cutting-edge technologies in modern biomedical applications. However, the in vivo use of motile probes has raised many concerns due to their low sensitivity and non-biocompatibility. As an alternative, biological enzymatic engines have received increased attention. In particular, ATPases, which belong to a class of motile enzymes that catalyze chemical metabolic reactions, have emerged as a promising motor due to their improved biocompatibility and performance. However, ATPases usually suffer from lower functional activity and are difficult to express recombinantly in bacteria relative to their conventional and synthetic competitors. Here, we report a novel functional modified ATPase with both a simple purification protocol and enhanced motile activity. For this mutant ATPase, a new bacterial subcloning method was established. The ATPase-encoding sequence was redesigned so that the mutant ATPase could be easily produced in an Escherichia coli system. The modified thermophilic F1-ATPase (mTF1-ATPase) demonstrated 17.8unit/mg ATPase activity. We propose that derivatives of our ATPase may enable the development of novel in vitro and in vivo synthetic medical diagnostics, as well as therapeutics.
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http://dx.doi.org/10.1016/j.jbiotec.2015.04.022DOI Listing
August 2015

Recycling process for recovery of gallium from GaN an e-waste of LED industry through ball milling, annealing and leaching.

Environ Res 2015 Apr 11;138:401-8. Epub 2015 Mar 11.

Institute for Advanced Engineering (IAE) Advanced Materials & Processing Center, Yongin-Si 449-863, Republic of Korea. Electronic address:

Waste dust generated during manufacturing of LED contains significant amounts of gallium and indium, needs suitable treatment and can be an important resource for recovery. The LED industry waste dust contains primarily gallium as GaN. Leaching followed by purification technology is the green and clean technology. To develop treatment and recycling technology of these GaN bearing e-waste, leaching is the primary stage. In our current investigation possible process for treatment and quantitative leaching of gallium and indium from the GaN bearing e-waste or waste of LED industry dust has been developed. To recycle the waste and quantitative leaching of gallium, two different process flow sheets have been proposed. In one, process first the GaN of the waste the LED industry dust was leached at the optimum condition. Subsequently, the leach residue was mixed with Na2CO3, ball milled followed by annealing, again leached to recover gallium. In the second process, the waste LED industry dust was mixed with Na2CO3, after ball milling and annealing, followed acidic leaching. Without pretreatment, the gallium leaching was only 4.91 w/w % using 4M HCl, 100°C and pulp density of 20g/L. After mechano-chemical processing, both these processes achieved 73.68 w/w % of gallium leaching at their optimum condition. The developed process can treat and recycle any e-waste containing GaN through ball milling, annealing and leaching.
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http://dx.doi.org/10.1016/j.envres.2015.02.027DOI Listing
April 2015

Evaluation of the formation of a junctional DNA nanostructure through annealing curve analysis.

Biochem Biophys Res Commun 2015 Feb 15;457(4):542-6. Epub 2015 Jan 15.

School of Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, South Korea; SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, 440-746, South Korea. Electronic address:

During the self-assembly of different numbers of oligonucleotides comprising junctional DNA nanostructures, a change in environmental variables (e.g., temperature or salt concentration) has a substantial influence on the final products. Further, distinctive annealing temperatures of oligonucleotides are observed depending on the state of hybridization. Here, we present an evaluation of the annealing characteristics of oligonucleotides for the formation of a simple junctional DNA nanostructure using an annealing curve analysis. This method may be useful for analyzing the formation of complex junctional DNA nanostructures.
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http://dx.doi.org/10.1016/j.bbrc.2015.01.020DOI Listing
February 2015

X-DNA origami-networked core-supported lipid stratum.

Langmuir 2015 Jan 13;31(3):912-6. Epub 2015 Jan 13.

School of Chemical Engineering and ‡SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University , Suwon 440-746, South Korea.

DNA hydrogels are promising materials for various fields of research, such as in vitro protein production, drug carrier systems, and cell transplantation. For effective application and further utilization of DNA hydrogels, highly effective methods of nano- and microscale DNA hydrogel fabrication are needed. In this respect, the fundamental advantages of a core-shell structure can provide a simple remedy. An isolated reaction chamber and massive production platform can be provided by a core-shell structure, and lipids are one of the best shell precursor candidates because of their intrinsic biocompatibility and potential for easy modification. Here, we demonstrate a novel core-shell nanostructure made of gene-knitted X-shaped DNA (X-DNA) origami-networked gel core-supported lipid strata. It was simply organized by cross-linking DNA molecules via T4 enzymatic ligation and enclosing them in lipid strata. As a condensed core structure, the DNA gel shows Brownian behavior in a confined area. It has been speculated that they could, in the future, be utilized for in vitro protein synthesis, gene-integration transporters, and even new molecular bottom-up biological machineries.
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http://dx.doi.org/10.1021/la503754eDOI Listing
January 2015

Self-illuminative cascade-reaction-driven anticancer therapeutic cassettes made of cooperatively interactive nanocomplexes.

Colloids Surf B Biointerfaces 2015 Feb 15;126:580-4. Epub 2014 Dec 15.

School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea; SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea. Electronic address:

Therapeutic options based on near-infrared (NIR) wavelengths have attracted attention owing to in vivo lowest-background interventions and the development of several nano-architectures with localized surface plasmon resonance. Because of their limited tissue penetration, the clinical use of NIR light-driven treatments is not widespread; this technology is inapplicable to infection sites in the deeper areas of internal tissues. In this study, we demonstrate a self-illuminative therapeutic cassette able to exert anticancer effects via a series of enzymatic, chemical, and optical cooperative cascade reactions. It consists of (1) NIR-illuminative nanocomplexes and (2) NIR-sensitive therapeutic cassettes, which demonstrate a 60% chemically-induced killing effect in a prostate cancer model without external NIR irradiation. This technology can also be actively exploited as an imaging agent due to adaptation of a self-illuminating nanocomplex. Consequently, these novel therapeutic cassettes, which work not only as a powerful internal NIR stimulant, but also as a biological imaging platform, provide a new rational design concept for biomedical use.
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http://dx.doi.org/10.1016/j.colsurfb.2014.12.011DOI Listing
February 2015

Elevated plasma pentraxin 3 and its association with retinal vein occlusion.

Korean J Ophthalmol 2014 Dec 19;28(6):460-5. Epub 2014 Nov 19.

Department of Ophthalmology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

Purpose: To evaluate plasma pentraxin 3 (PTX3) in patients with retinal vein occlusion (RVO), and investigate the possibility of its role as a predictive biomarker.

Methods: Nested case-control study. The study included 57 patients with RVO and 45 age- and gender-matched subjects without RVO as controls. Plasma PTX3 and C-reactive protein concentration were measured in both groups a posteriori from frozen samples by using an enzyme-linked immunosorbent assay kit.

Results: The measured PTX3 value for the RVO group was 1,508 ± 1,183 pg/mL (mean ± standard deviation) and 833 ± 422 pg/mL for the controls (p < 0.001). There was no significant difference in PTX3 levels between patients with central retinal vein occlusion and branched retinal vein occlusion (1,468 ± 1,300 vs. 1,533 ± 1,121 pg/mL; p = 0.818).

Conclusions: Our data seems to support the role of chronic inflammation and ischemia in the development of RVO. It is possible that PTX3 can be used as a diagnostic biomarker of RVO.
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http://dx.doi.org/10.3341/kjo.2014.28.6.460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239464PMC
December 2014

Apurinic/apyrimidinic endonuclease 1 on aging-associated deteriorations in rat kidneys.

Free Radic Res 2015 Jan 22;49(1):95-101. Epub 2014 Nov 22.

Department of Anatomy, College of Medicine, Chosun University , Gwangju , Republic of Korea.

We have reported a possible involvement of apurinic/apyrimidinic endonuclease 1 (APE1), one of the DNA repair pathways, in various nephropathy models and found that there is a close connection between APE1 and p53-dependent apoptosis. Therefore, we investigated the changes of APE in aging rat kidney since aging is the consequence of increased susceptibility to apoptosis and impaired repair. Characteristics of chronological aging were compared among 6-, 24- and 28-month-old male Sprague-Dawley rats. Serum blood urea nitrogen and creatinine were measured for renal function. Western blot assay was compared for p53, bax, cleaved caspase 3, rH2AX, and APE1. Immunohistochemical staining of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and APE1 was performed. Cellular senescence was checked by beta-galactosidase staining. Compared with young rats, aged rats showed significant increase in creatinine level with cellular senescence in the proximal convoluted tubules confirmed by beta-galactosidase staining. All the checked variables were significantly increased with aging: 1) increased p53, bax, and caspase 3 may activate the apoptotic pathway, 2) increased rH2AX and 8-OHdG immunolocalization in the proximal convoluted tubules might mean augmented DNA damage, and 3) increased APE1 might be caused by the immunoreactivity in the distal convoluted tubules while decreased in the proximal convoluted tubules. These results suggested that APE1 might have little protective effects on p53-dependent apoptosis irrespective of DNA repair activities in aged renal proximal tubules. Therefore, researchers should use older animals than 24-month-old rats in future studies for investigating the relationship between the apoptosis and DNA repair in the aging kidneys.
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http://dx.doi.org/10.3109/10715762.2014.981261DOI Listing
January 2015

Germanium microflower-on-nanostem as a high-performance lithium ion battery electrode.

Sci Rep 2014 Nov 3;4:6883. Epub 2014 Nov 3.

School of Civil, Environmental and Architectural Engineering, Korea University, Seoul 136-713, Korea.

We demonstrate a new design of Ge-based electrodes comprising three-dimensional (3-D) spherical microflowers containing crystalline nanorod networks on sturdy 1-D nanostems directly grown on a metallic current collector by facile thermal evaporation. The Ge nanorod networks were observed to self-replicate their tetrahedron structures and form a diamond cubic lattice-like inner network. After etching and subsequent carbon coating, the treated Ge nanostructures provide good electrical conductivity and are resistant to gradual deterioration, resulting in superior electrochemical performance as anode materials for LIBs, with a charge capacity retention of 96% after 100 cycles and a high specific capacity of 1360 mA h g(-1) at 1 C and a high-rate capability with reversible capacities of 1080 and 850 mA h g(-1) at the rates of 5 and 10 C, respectively. The improved electrochemical performance can be attributed to the fast electron transport and good strain accommodation of the carbon-filled Ge microflower-on-nanostem hybrid electrode.
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http://dx.doi.org/10.1038/srep06883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217107PMC
November 2014

Transcription elongation factor ELL2 drives Ig secretory-specific mRNA production and the unfolded protein response.

J Immunol 2014 Nov 19;193(9):4663-74. Epub 2014 Sep 19.

Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261; and

Differentiation of B cells into Ab-secreting cells induces changes in gene transcription, IgH RNA processing, the unfolded protein response (UPR), and cell architecture. The transcription elongation factor eleven nineteen lysine-rich leukemia gene (ELL2) stimulates the processing of the secreted form of the IgH mRNA from the H chain gene. Mice (mus musculus) with the ELL2 gene floxed in either exon 1 or exon 3 were constructed and crossed to CD19-driven cre/CD19(+). The B cell-specific ELL2 conditional knockouts (cKOs; ell2(loxp/loxp) CD19(cre/+)) exhibit curtailed humoral responses both in 4-hydroxy-3-nitrophenyl acetyl-Ficoll and in 4-hydroxy-3-nitrophenyl acetyl-keyhole limpet hemocyanin immunized animals; recall responses were also diminished. The number of immature and recirculating B cells in the bone marrow is increased in the cKOs, whereas plasma cells in spleen are reduced relative to control animals. There are fewer IgG1 Ab-producing cells in the bone marrow of cKOs. LPS ex vivo-stimulated B220(lo)CD138(+) cells from ELL2-deficient mouse spleens are 4-fold less abundant than from control splenic B cells; have a paucity of secreted IgH; and have distended, abnormal-appearing endoplasmic reticulum. IRE1α is efficiently phosphorylated, but the amounts of Ig κ, ATF6, BiP, Cyclin B2, OcaB (BOB1, Pou2af1), and XBP1 mRNAs, unspliced and spliced, are severely reduced in ELL2-deficient cells. ELL2 enhances the expression of BCMA (also known as Tnfrsf17), which is important for long-term survival. Transcription yields from the cyclin B2 and the canonical UPR promoter elements are upregulated by ELL2 cDNA. Thus, ELL2 is important for many aspects of Ab secretion, XBP1 expression, and the UPR.
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http://dx.doi.org/10.4049/jimmunol.1401608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201982PMC
November 2014