Publications by authors named "Jong Seung Kim"

356 Publications

Correction: Post-synthetic modifications in porous organic polymers for biomedical and related applications.

Chem Soc Rev 2022 Aug 1;51(15):6864. Epub 2022 Aug 1.

Department of Chemistry, Korea University, Seoul 02841, Korea.

Correction for 'Post-synthetic modifications in porous organic polymers for biomedical and related applications' by Ji Hyeon Kim , , 2022, , 43-56, https://doi.org/10.1039/D1CS00804H.
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http://dx.doi.org/10.1039/d2cs90059aDOI Listing
August 2022

An Activity-Based Fluorescent Probe for Imaging Fluctuations of Peroxynitrite (ONOO ) in the Alzheimer's Disease Brain.

Angew Chem Int Ed Engl 2022 Jul 5:e202206894. Epub 2022 Jul 5.

Department of Chemistry, Korea University, Seoul, 02841, Korea.

Peroxynitrite (ONOO ) plays a critical role in Alzheimer's disease (AD). To reveal the ONOO influx in AD brains, an activatable activity-based fluorescence probe Rd-DPA3 was designed by a structure-modulated strategy. Taking advantage of ONOO -initiated two-step cascade reactions of a novel chemical trigger, Rd-DPA3 specifically responds to ONOO in 0.3 mM of other reactive oxygen species (ROS) and varied proteins, and gives an intensive fluorescence enhancement (F/F =50). Moreover, with its mitochondria-targeting ability, Rd-DPA3 can be used to efficiently monitor the alternations of intracellular ONOO levels in cerebral cells during oxidative stress. Significantly, due to NIR emission and good blood-brain barrier (BBB) crossing ability, Rd-DPA3 is suitable for in vivo imaging of cerebral ONOO influx and illustrating an age-dependent accumulation of ONOO in AD mice brains.
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http://dx.doi.org/10.1002/anie.202206894DOI Listing
July 2022

Prevalence and comorbidities of bronchiolitis in adults: A population-based study in South Korea.

Medicine (Baltimore) 2022 Jun 24;101(25):e29551. Epub 2022 Jun 24.

Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Medical School, Jeonju, South Korea.

Abstract: Bronchiolitis generally refers to inflammation and/or fibrosis of the non-cartilaginous small airways located approximately from the 8th airway generation down to the terminal and respiratory bronchioles. In contrast to young children, the frequency of small airway infection in adult bronchiolitis appears less frequent and a number of other pathophysiological conditions have been implicated in adult bronchiolitis. However, little information is available on the exact medical burden of bronchiolitis such as its prevalence and comorbidities in the adult population. The aim of this study is to elucidate the prevalence and comorbidities of bronchiolitis. We used the Korea National Health Insurance Service-National Sample Cohort, which provides data for 1,000,000 individuals out of the entire population by 2% stratified random sampling according to age, sex, residential area, and level of household income. We defined the cause of bronchiolitis other than acute infection as a patient with diagnostic code J448 or J684 and over 20 years of age who visited a clinic or hospital in South Korea. Then, 1:1 propensity score matching was performed to define a non-bronchiolitis (control) group to compare the comorbidities and mortality in the 2 groups. The overall prevalence of bronchiolitis was 688 cases/1,000,000 population during the study period (95% confidence interval, 625-751). The most common comorbid clinical condition in adults with bronchiolitis was rhinitis (52.3%), followed by bronchial asthma (52.23%), hypertension (43.69%), gastroesophageal reflux disease (30.56%), sinusitis (28.72%), diabetes (22.77%), and osteoporosis (17.85%). Other common bronchiolitis-associated comorbidities were cerebrovascular disease (16.86%), angina (14.37%), peripheral vascular disease (13.42%), congestive heart failure (11.9%), and malignancy in any organ (10.6%). Healthcare costs for bronchiolitis increased steeply during the same period. Malignancy in any organ was the leading cause of mortality in the patient group, followed by bronchiolitis itself. Further larger prospective multiethnic cohort studies should be carried out in the near future.
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http://dx.doi.org/10.1097/MD.0000000000029551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276453PMC
June 2022

Rationally designed Ru(ii)-metallacycle chemo-phototheranostic that emits beyond 1000 nm.

Chem Sci 2022 Jun 18;13(22):6541-6549. Epub 2022 May 18.

Key Laboratory of Pesticides and Chemical Biology, Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University Wuhan 430079 China

Ruthenium complexes are emerging as potential complements to platinum drugs. They also show promise as photo-diagnostic and therapeutic agents. However, most ruthenium species studied to date as potential drugs are characterized by short excitation/emission wavelengths. This limits their applicability for deep-tissue fluorescence imaging and light-based therapeutic treatments. Here, we report a Ru(ii) metallacycle (Ru1100) that emits at ≥1000 nm. This system possesses excellent deep-tissue penetration capability (∼7 mm) and displays good chemo-phototherapeutic performance. studies revealed that Ru1100 benefits from good cellular uptake and produces a strong anticancer response against several cancer cell lines, including a cisplatin-resistant A549 cell line (IC = 1.6 μM 51.4 μM for cisplatin). On the basis of studies, it is concluded that Ru1100 exerts its anticancer action by regulating cell cycle progression and triggering cancer cell apoptosis. studies involving the use of a nanoparticle formulation served to confirm that Ru1100 allows for high-performance NIR-II fluorescence imaging-guided precise chemo-phototherapy in the case of A549 tumour mouse xenografts with no obvious side effects. This work thus provides a paradigm for the development of long-wavelength emissive supramolecular theranostic agents based on ruthenium.
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http://dx.doi.org/10.1039/d2sc01518hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172562PMC
June 2022

Immunosonodynamic Therapy Designed with Activatable Sonosensitizer and Immune Stimulant Imiquimod.

ACS Nano 2022 Jun 17. Epub 2022 Jun 17.

Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.

Sonodynamic therapy (SDT) has garnered extensive attention as a noninvasive treatment for deep tumors. Furthermore, imiquimod (R837), an FDA-approved toll-like receptor 7 agonist, is commonly used in clinical settings as an immune adjuvant. We prepared an activatable sonodynamic sensitizer platform (MR) based on glutathione-sensitive disulfide bonds linking Leu-MB, the reduced form of methylene blue (MB), and R837 to achieve efficient combinatory SDT and immunotherapy for tumors without harming normal tissues. We also used the amphiphilic polymer CPMH-PEG to create self-assembled MB-R837-PEG (MRP) nanoparticles for immunosonodynamic therapy (iSDT). iSDT is a cancer treatment that combines activatable SDT and immunotherapy. Our iSDT demonstrated an excellent sonodynamic effect only at the tumor site, demonstrating high specificity in killing tumor cells when compared to SDT reported in the literature. The iSDT improves its tumor-killing effect by inducing an immune response, which is accomplished by secreted immune adjuvants in the tumor site. MRP was selectively activated by glutathione in the tumor microenvironment to release MB and R837, exhibiting excellent antitumor sonodynamic and immune responses. In addition, when combined with an α-PD-L1 antibody for immune checkpoint blockade, this therapy effectively inhibited tumor metastasis. Furthermore, mice treated with iSDT and α-PD-L1 antibody did not develop tumors even after tumor reinoculation, indicating that long-term immune memory was achieved. The concept of sonodynamic sensitizer preparation as a next-generation iSDT based on a noninvasive synergistic therapeutic modality applicable in the near future is presented in this study.
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http://dx.doi.org/10.1021/acsnano.2c03395DOI Listing
June 2022

Photocatalytic Superoxide Radical Generator that Induces Pyroptosis in Cancer Cells.

J Am Chem Soc 2022 06 16;144(25):11326-11337. Epub 2022 Jun 16.

Department of Chemistry, Korea University, Seoul 02841, Korea.

Pyroptosis, a newly characterized form of immunogenic cell death, is attracting increasing attention as a promising approach to cancer immunotherapy. However, biocompatible strategies to activate pyroptosis remain rare. Here, we show that a photocatalytic superoxide radical (O) generator, , triggers pyroptosis in cancer cells. was designed to take advantage of an intramolecular triplet-ground state splitting energy modulation approach. Detailed studies revealed that the pyroptosis triggered by under conditions of photoexcitation proceeds through a caspase-3/gasdermin E (GSDME) pathway rather than via canonical processes involving caspase-1/gasdermin-D (GSDMD). was found to function via a partial-O-recycling mode of action and to trigger cell pyroptosis and provide for effective cancer cell ablation even under conditions of hypoxia (≤2% O). In the case of T47D 3D multicellular spheroids, good antitumor efficiency and stemness inhibition are achieved. This work highlights how photocatalytic chemistry may be leveraged to develop effective pyroptosis-inducing agents.
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http://dx.doi.org/10.1021/jacs.2c03256DOI Listing
June 2022

A molecular recognition platform for the simultaneous sensing of diverse chemical weapons.

Chem Sci 2022 Apr 23;13(16):4523-4532. Epub 2022 Mar 23.

Department of Chemistry, Korea University Seoul 02841 Korea

Chemical warfare agents (CWAs) such as phosgene and nerve agents pose serious threats to our lives and public security, but no tools can simultaneously screen multiple CWAs in seconds. Here, we rationally designed a robust sensing platform based on 8-cyclohexanyldiamino-BODIPY (BODIPY-DCH) to monitor diverse CWAs in different emission channels. -cyclohexanyldiamine as the reactive site provides optimal geometry and high reactivity, allowing -BODIPY-DCH to detect CWAs with a quick response and high sensitivity, while -BODIPY-DCH has much weaker reactivity to CWAs due to intramolecular H-bonding. Upon reaction with phosgene, -BODIPY-DCH was rapidly converted to imidazolone BODIPY (<3 s), triggering green fluorescence with good sensitivity (LOD = 0.52 nM). -BODIPY-DCH coupled with nerve agent mimics, affording a blue fluorescent 8-amino-BODIPY tautomer. Furthermore, a portable test kit using -BODIPY-DCH displayed an instant response and low detection limits for multiple CWAs. This platform enables rapid and highly sensitive visual screening of various CWAs.
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http://dx.doi.org/10.1039/d2sc00299jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020178PMC
April 2022

A case of large ethmoid bulla causing chronic rhinosinusitis: 'Bulla bullosa'.

Ear Nose Throat J 2022 Jun 1:1455613221106223. Epub 2022 Jun 1.

Department of Otolaryngology-Head and Neck Surgery, 90158Jeonbuk National University Medical School, Jeonju, Korea.

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http://dx.doi.org/10.1177/01455613221106223DOI Listing
June 2022

2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy.

Bioact Mater 2022 Aug 18;14:76-85. Epub 2021 Dec 18.

Department of Chemistry, Korea University, Seoul, 02841, South Korea.

An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation, tumor progression and metastasis. This makes iron metabolism an attractive therapeutic target. Unfortunately, current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities. We report here a dual-therapeutic prodrug, , that allows for iron chelation chemo-photothermal cancer therapy. This prodrug takes advantage of the clinically approved iron chelator deferasirox (ExJade®) and the topoisomerase 2 inhibitor, doxorubicin (DOX). Loading onto ultrathin 2D TiC MXene nanosheets produces a construct, , that allows the iron chelation and chemotherapeutic functions of to be photo-activated at the tumor sites, while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%. Antitumor mechanistic investigations reveal that upon activation, serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor (TfR). A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both and . The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.
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http://dx.doi.org/10.1016/j.bioactmat.2021.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892152PMC
August 2022

Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes.

Bioact Mater 2022 Jul 9;13:239-248. Epub 2021 Nov 9.

Department of Chemistry, Korea University, Seoul, 02841, South Korea.

The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of β-amyloid (Aβ), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aβ species have been developed, with increasing binding affinities. In the current work, two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ fibrils -while concurrently preventing poor aqueous solubility- biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (  = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue . These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.
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http://dx.doi.org/10.1016/j.bioactmat.2021.10.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845109PMC
July 2022

Mitochondrial targeted AIEgen phototheranostics for bypassing immune barrier via encumbering mitochondria functions.

Biomaterials 2022 04 19;283:121409. Epub 2022 Feb 19.

Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea. Electronic address:

Photodynamic therapy combined with immunogenic cell death has been proposed to overcome the unsolvable problems of single therapy, such as high levels of tumor recurrence and treatment resistance of tumors. Previous works on this theme have mostly concentrated on endoplasmic reticulum (ER)-stressed damage-associated molecular patterns (DAMPs), ignoring the secretion and function of mitochondria-related DAMPs. Herein, our work reports two intersystem crossing photosensitizers based on well-designed multiarylpyrrole structures and draws valuable attention to mitochondria-related DAMP-TFAM (mitochondrial transcription factor) when cancer cells are under forceful oxidative stress. The tumors vanished, and immunogenic experiments were applied to illuminate the advantages of double treatment. Our discovery of new mitochondria-related DAMPs compensates for the lack of ER-stressed DAMPs and offers an innovative target for immunity therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2022.121409DOI Listing
April 2022

Effectiveness of Intratympanic Dexamethasone Injection for Tinnitus Treatment: A Systematic Review and Meta-Analysis.

Clin Exp Otorhinolaryngol 2022 Feb 12;15(1):91-99. Epub 2022 Feb 12.

Department of Otorhinolaryngology-Head and Neck Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Kroea.

Objectives: Intratympanic dexamethasone injection (ITDI) has been introduced as a treatment option for subjective tinnitus. However, the effects of ITDI on patients with tinnitus remain unclear. In the present systematic review and metaanalysis, we evaluated the effectiveness of ITDI for tinnitus treatment.

Methods: We searched Medline, the Cochrane Central Register of Controlled Trials, and Embase. Four double-blind randomized controlled trials that tested the efficacy of ITDI compared with a placebo were deemed eligible for a quantitative meta-analysis, while four prospective studies and seven retrospective studies reporting the effectiveness of ITDI on tinnitus treatment were included in a qualitative synthesis.

Results: In the four studies included in the quantitative meta-analysis, ITDI did not show evidence of tinnitus improvement compared with placebo (odds ratio [OR], 1.38; 95% confidence interval, 0.53-3.61). In the 11 studies included in the qualitative synthesis, seven retrospective studies without controls reported rates of tinnitus improvement after ITDI ranging from 35.9% to 91.3%. In the four prospective studies with controls, ITDI seemed to be effective when combined with other drugs for tinnitus treatment.

Conclusion: ITDI alone did not show a significant effect for treating tinnitus compared with placebo. However, the potential of combination treatment of ITDI with other drugs for tinnitus therapy should be further studied in more systematic research.
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http://dx.doi.org/10.21053/ceo.2021.01459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901947PMC
February 2022

Harnessing GLUT1-Targeted Pro-oxidant Ascorbate for Synergistic Phototherapeutics.

Angew Chem Int Ed Engl 2022 04 3;61(17):e202110832. Epub 2022 Mar 3.

Department of Chemistry, Korea University, Seoul, 02841, Korea.

Despite extensive efforts to realize effective photodynamic therapy (PDT), there is still a lack of therapeutic approaches concisely structured to mitigate the major obstacles of PDT in clinical applications. Herein, we report a molecular strategy exploiting ascorbate chemistry to enhance the efficacy of PDT in cancer cells overexpressing glucose transporter 1 (GLUT1). AA-EtNBS, a 5-O-substituted ascorbate-photosensitizer (PS) conjugate, undergoes a reversible structural conversion of the ascorbate moiety in the presence of reactive oxygen species (ROS) and glutathione (GSH), thereby promoting its uptake in GLUT1-overexpressed KM12C colon cancer cells and perturbing tumor redox homeostasis, respectively. Due to the unique pro-oxidant role of ascorbate in tumor environments, AA-EtNBS effectively sensitized KM12C cancer cells prior to PS-mediated generation of superoxide radicals under near-infrared (NIR) illumination. AA-EtNBS successfully exhibited GLUT1-targeted synergistic therapeutic efficacy during PDT both in vitro and in vivo. Therefore, this study outlines a promising strategy employing ascorbate both as a targeting unit for GLUT1-overexpressed cancer cells and redox homeostasis destruction agent, thereby enhancing therapeutic responses towards anticancer treatment when used in conjunction with conventional PDT.
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http://dx.doi.org/10.1002/anie.202110832DOI Listing
April 2022

DNA-Damage-Response-Targeting Mitochondria-Activated Multifunctional Prodrug Strategy for Self-Defensive Tumor Therapy.

Angew Chem Int Ed Engl 2022 04 19;61(16):e202117075. Epub 2022 Feb 19.

Department of Chemistry, Korea University, Seoul, 02841, Korea.

We report a novel multifunctional construct, M1, designed explicitly to target the DNA damage response in cancer cells. M1 contains both a floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor combined with a GSH-sensitive linker. Further conjugation of the triphenylphosphonium moiety allows M1 to undergo specific activation in the mitochondria, where mitochondria-mediated apoptosis is observed. Moreover, M1 has enormous effects on genomic DNA ascribed to FUDR's primary function of impeding DNA/RNA synthesis combined with diminishing PP2A-activated DNA repair pathways. Importantly, mechanistic studies highlight the PP2A obtrusion in FUDR/5-fluorouracil (5-FU) therapy and underscore the importance of its inhibition to harbor therapeutic potential. HCT116 cell xenograft-bearing mice that have a low response rate to 5-FU show a prominent effect with M1, emphasizing the importance of DNA damage response targeting strategies using tumor-specific microenvironment-activatable systems.
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http://dx.doi.org/10.1002/anie.202117075DOI Listing
April 2022

Metal-based anticancer agents as immunogenic cell death inducers: the past, present, and future.

Chem Soc Rev 2022 Feb 21;51(4):1212-1233. Epub 2022 Feb 21.

Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712-1224, USA.

Cancer is the deadliest disease in the world behind heart disease. Sadly, this remains true even as we suffer the ravages of the Covid-19 pandemic. Whilst current chemo- and radiotherapeutic treatment strategies have significantly improved the patient survival rate, disease reoccurrence continues to pose a deadly risk for all too many patients. Incomplete removal of tumour cells from the body increases the chances of metastasis and developing resistance against current treatments. Immunotherapy represents a therapeutic modality that has helped to overcome these limitations in recent decades. However, further progress is needed. So-called immunogenic cell death (ICD) is a recently discovered and unique mode of cell death that could trigger this necessary further progress. ICD involves stimulation of a tumour-specific immune response as a downstream effect. Facilitated by certain treatment modalities, cells undergoing ICD can trigger the IFN-γ mediated immune response involving cytotoxic T cells (CTLs) and γδ T cells that eradicate residual tumour cells. In recent years, there has been a significant increase in the number of small-molecules being tested as potential ICD inducers. A large number of these ICD inducers are metal-based complexes. In fact, anticancer metal drugs based on Pt, Ru, Ir, Cu, and Au are now known to give rise to an immune response against tumour cells as the result of ICD. Advances have also been made in terms of exploiting combinatorial and delivery strategies. In favourable cases, these approaches have been shown to increase the efficacy of otherwise ICD "silent" metal complexes. Taken in concert, rationally designed novel anticancer metal complexes that can act as ICD inducers show promise as potential new immunotherapies for neoplastic disease. This Tutorial Review will allow the readers to assess the progress in this fast-evolving field thus setting the stage for future advances.
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http://dx.doi.org/10.1039/d1cs00417dDOI Listing
February 2022

Forum on Biospecies Sensors.

ACS Appl Bio Mater 2021 03;4(3):2231-2232

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http://dx.doi.org/10.1021/acsabm.1c00164DOI Listing
March 2021

Phenylthiourea-Conjugated BODIPY as an Efficient Photosensitizer for Tyrosinase-Positive Melanoma-Targeted Photodynamic Therapy.

ACS Appl Bio Mater 2021 03 24;4(3):2120-2127. Epub 2020 Nov 24.

Department of Chemistry, Korea University, Seoul 02841, Korea.

Melanoma is the most threatening form of metastatic skin cancer that develops from melanocytes and causes a large majority of deaths due to poor therapeutic prognosis. It has significant limitations in treatment because it shows great resistance to chemotherapy, radiotherapy, and other therapeutic methods. A noninvasive and clinically accepted therapeutic modality, photodynamic therapy (PDT), is a promising treatment option, but it is limitedly applied for melanoma skin cancer treatment. This is because most of the photosensitizers are unlikely to be expected to have a remarkable effect on melanoma due to drug efflux by melanin pigmentation and intrinsic antioxidant defense mechanisms. Moreover, melanin is a dominant absorber in the spectral region of 500-600 nm that can cause the decreased photoreaction efficiency of photosensitizers. Herein, to overcome these drawbacks, we have developed a phenylthiourea-conjugated BODIPY photosensitizer () for tyrosinase-positive melanoma-targeted PDT. In light of our results, it exhibited an enhanced cytotoxic efficacy compared to BDP, a parallel PDT agent that absence of phenylthiourea unit. shows outstanding effects of increased oxidative stress by an enhanced cellular uptake of the tyrosinase positive melanoma cell line (B16F10). This work presents increased therapeutic efficacy through the combined therapeutic approach, enabling enhanced reactive oxygen species (ROS) generation as well as overcoming the critical limitations of melanoma.
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http://dx.doi.org/10.1021/acsabm.0c01322DOI Listing
March 2021

Nanoliposomal Ratiometric Fluorescent Probe toward ONOO Flux.

ACS Appl Bio Mater 2021 03 6;4(3):2080-2088. Epub 2020 Nov 6.

Department of Chemistry, Korea University, Seoul 02841, Korea.

Peroxynitrite (ONOO), a powerful biological oxidant, is produced in the mitochondria and reacts with many biomolecular targets under various pathological conditions, leading to a range of disease states. In this work, we developed a nanoliposome-encapsulated ratiometrically fluorescent probe () based on a hemicyanine structure obtained by facile synthesis. Upon reaction with ONOO, the oxidation and hydrolysis of a π-conjugation system within the nanoliposome triggers a ratiometrically fluorescent response and a large-scale emission shift (238 nm), which provides a specific and sensitive means for the ONOO detection. Moreover, we have performed DFT calculation at the 6-31+G(d,p) level using a suite of programs to obtain insights into the chemical structure optical properties of . In addition, the practical applications of the nanoprobe to image exogenous and endogenous ONOO were achieved further in live cells and animals triumphantly.
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http://dx.doi.org/10.1021/acsabm.0c01178DOI Listing
March 2021

Fluorescent Probe for Monitoring Hydrogen Peroxide in COX-2-Positive Cancer Cells.

ACS Appl Bio Mater 2021 03 3;4(3):2073-2079. Epub 2020 Nov 3.

Department of Chemistry, Korea University, Seoul 02841, South Korea.

Hydrogen peroxide (HO), an important marker for oxidative stress, plays a vital role in cellular biological functions. Overproduction of HO causes oxidative damage to cellular functions and promotes cancer and other neurodegenerative diseases. Also, cyclooxygenase-2 (COX-2) enzyme is known to be expressed in several cancer types and exerts multifaceted roles in carcinogenesis and resistance to cancer treatment. Hence, it is important to monitor the HO concentration changes in the COX-2-expressing cancer cells. Herein, we have developed a molecular fluorescent ratiometric HO-responsive probe () composed of indomethacin (COX-2 inhibitor) conjugated with 1,8-napthalimide boronate ester as fluorescent reporter through a chemical linker. The probe was capable of imaging the endogenous HO in COX-2 overexpressing cancer cell lines (A549, LoVo, HT29, and Caco-2). Further studies revealed the critical role of the indomethacin moiety in the cellular uptake behavior of in COX-2-overexpressing cancer cells. Collectively, our results demonstrated as a COX-2-positive cancer-targeting sensitive ratiometric fluorescent probe (/) for HO imaging and showed its promising biological applications in the future.
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http://dx.doi.org/10.1021/acsabm.0c01135DOI Listing
March 2021

Binary Prodrug of Dichloroacetic Acid and Doxorubicin with Enhanced Anticancer Activity.

ACS Appl Bio Mater 2021 03 8;4(3):2026-2032. Epub 2020 Jun 8.

Department of Chemistry, Korea University, Seoul 02841, Korea.

The inevitable challenge in conventional chemotherapy is to deliver the anticancer drugs to the dense population of tumors cells while minimizing the drug-associated side effects on the normal cells. Cancer cells' preference for glycolysis for energy production is well recognized. Intuitively, taking advantage of such cancer-associated metabolism would be a promising strategy for anticancer drug delivery with minimal side effects. In this investigation, we have designed a binary prodrug as a sequential drug delivery regimens to realize the combination therapy for cancer. As cancer cells exhibit abrupt metabolism with elevated pyruvate dehydrogenase kinase (PDK) activity, dichloroacetic acid (DCA, a well-known PDK inhibitor) was used in combination with anticancer drug doxorubicin (DOX). The designed molecular prodrug was activated selectively by cancer-associated esterase to deliver DCA and DOX, respectively, and induced synergetic effects. Hence, sequential targeted delivery of molecular prodrug offers a promising approach to overcome the offside drug toxicity, pharmacokinetics, and biodistribution of individuals and provide an alternative option for cancer treatment.
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http://dx.doi.org/10.1021/acsabm.0c00443DOI Listing
March 2021

Association of sudden sensorineural hearing loss with increased risk of insomnia: a nationwide population-based cohort study.

J Clin Sleep Med 2022 05;18(5):1335-1342

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Jeonbuk National University, Jeonju, Korea.

Study Objectives: To evaluate the risk of insomnia in patients with sudden sensorineural hearing loss (SSNHL).

Methods: A retrospective propensity score-matched cohort study was conducted using a nationwide representative sample from the National Sample Cohort 2002-2013 data from the Korea National Health Insurance Service. The SSNHL group (n = 631) included patients diagnosed with SSNHL between January 2002 and December 2005. The comparison group (4 controls for every patient with SSNHL, n = 2,524) was selected using propensity score matching, according to sociodemographic factors and the year of enrollment. Each patient was monitored until 2013. Survival analysis, log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of insomnia for each group.

Results: Among the 3,155 individuals included in the study population (male, 48.6%), the overall incidence of insomnia during the 11-year follow-up was 1.4-fold higher in the SSNHL group than in the non-SSNHL group (106.3 vs 138.3 per 10,000 person-years; adjusted HR, 1.38; 95% confidence interval [CI], 1.08-1.78). Moreover, the adjusted HRs for developing insomnia (depression, 3.33 [95% CI, 2.22-5.01]; anxiety, 1.78 [95% CI, 1.27-2.53]; tinnitus, 1.56 [95% CI, 1.2-2.03]; dizziness, 1.76 [95% CI, 1.27-2.44]) were higher in patients with comorbidities.

Conclusions: This observational study suggests that SSNHL is associated with an increased incidence of insomnia. Specifically, findings from this study show that patients with tinnitus, depression, anxiety, and dizziness had a higher risk of developing insomnia than those without tinnitus, depression, anxiety, and dizziness.

Citation: Yeo CD, Yeom SW, You YS, Kim JS, Lee EJ. Association of sudden sensorineural hearing loss with increased risk of insomnia: a nationwide population-based cohort study. . 2022;18(5):1335-1342.
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http://dx.doi.org/10.5664/jcsm.9864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059585PMC
May 2022

Endoscopic findings of dental implant found in the infundibulum showing the mucociliary clearance of the maxillary sinus.

Ear Nose Throat J 2022 Jan 2:1455613211062454. Epub 2022 Jan 2.

Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, 26714Jeonbuk National University, Jeon-ju, Korea.

A 53-year-old man with left facial pain was referred to our hospital. Nasal endoscopy revealed a purulent discharge at the left middle meatus and bulging of the uncinate process. Computed tomography demonstrated that the dental implant was blocking the left maxillary ostium. Functional endoscopic sinus surgery was performed under general anesthesia. After removal of the uncinate process, a yellowish purulent discharge in the left maxillary sinus discharged from the maxillary sinus. The presence of the dental implant in the infundibulum shows the direction of mucociliary clearance from the nasal sinus. This case indicates how our sinus clears a foreign body, and the direction in which the foreign body is removed.
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http://dx.doi.org/10.1177/01455613211062454DOI Listing
January 2022

Discovery of an Ultra-rapid and Sensitive Lysosomal Fluorescence Lipophagy Process.

Angew Chem Int Ed Engl 2022 03 14;61(11):e202116439. Epub 2022 Jan 14.

Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 61064, P. R. China.

Non-invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non-ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q-P-ARh dye, developed by us for the first time, can stain lysosomes at ultra-low concentrations (1.0 nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti-interference ability and ultrafast lysosomal staining ability (within 1.0 min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments.
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http://dx.doi.org/10.1002/anie.202116439DOI Listing
March 2022

Conditionally Activatable Photoredox Catalysis in Living Systems.

J Am Chem Soc 2022 01 28;144(1):163-173. Epub 2021 Dec 28.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, People's Republic of China.

The transformational effect of photoredox catalytic chemistries has inspired new opportunities, enabling us to interrogate nature in ways that are not possible otherwise and to unveil new biotechnologies in therapy and diagnosis. However, the deployment of artificial photoredox catalysis in living systems remains challenging, mired by the off-target risk and safety concerns of photocatalyst toxicity. Here, we present an appealing approach, namely conditionally activatable photoredox catalysis (ConAPC), and as a proof of concept design the first ConAPC architecture () based upon classic self-immolative chemistry, in which the inherent photocatalytic properties can be temporarily caged while the species becomes active only at the tumor sites via sensing to specific biomarkers. Such a masking strategy allows a spatial-temporal control of photoresponsivity and . In particular, for ConAPC design, a new biologically benign metal-free photocatalyst (), which is able to initiate NIR photoredox catalysis to manipulate the cellular electron pool in an O-independent mechanism of action, is identified. With this unique strategy, potent tumor-specific targeting photocatalytic eradication (TGI: 95%) is obtained in a mouse model. Impressively, favorable features such as high-resolution tumor recognition (SBR: 33.6) and excellent biocompatibility and safety are also achieved. This work therefore offers a new possibility for chemists to leverage artificial photocatalytic reactions toward the development of facile and intelligent photocatalytic theranostics.
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http://dx.doi.org/10.1021/jacs.1c07372DOI Listing
January 2022

ROS activated prodrug for ALDH overexpressed cancer stem cells.

Chem Commun (Camb) 2021 Dec 21;58(1):72-75. Epub 2021 Dec 21.

Department of Chemistry, Korea University, Seoul 02841, Korea.

Aldehyde dehydrogenase (ALDH), a cancer stem cell biomarker, is related to drug resistance. Co-treatment of anti-cancer drug (CPT) and ALDH inhibitor (DEAB) can overcome the drug resistance of cancer stem cells (CSCs) and finally cure cancers without relapse. We herein introduce a prodrug (DE-CPT) - consisting of 1,3-oxathiolane as an ROS responsive scaffold, and an aldehyde protecting group of DEAB - to deliver the CPT and DEAB upon reaction with ROS. From tests of the sphere-forming ability and CSC marker subpopulation, we found that DE-CPT efficiently decreases the CSCs population and kills the cancer cells.
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http://dx.doi.org/10.1039/d1cc05573aDOI Listing
December 2021

Post-synthetic modifications in porous organic polymers for biomedical and related applications.

Chem Soc Rev 2022 Jan 4;51(1):43-56. Epub 2022 Jan 4.

Department of Chemistry, Korea University, Seoul 02841, Korea.

Porous organic polymers (POPs) are prepared by crosslinked polymerization of multidimensional rigid aromatic building blocks. Generally, POPs can be classified into crystalline covalent organic frameworks (COFs) and other poorly crystalline or amorphous porous polymers. Due to their remarkable intrinsic properties, such as high porosity, stability, tunability, and presence of numerous building blocks, several new POPs are being developed for application across various scientific fields. The essential sensitive functional groups needed for specific applications are not sustained under harsh POP preparation conditions. The recently developed post-synthetic modification (PSM) strategies for POPs have enabled their advanced applications that are otherwise restricted. Owing to the advanced PSM strategies POPs have experienced a blossoming resurgence with diverse functions, particularly in biomedical applications, such as bioimaging tools, drugs, enzymes, gene or protein delivery systems, phototherapy, and cancer therapy. This tutorial review focuses on the recently developed PSM strategies for POPs, especially for biomedical applications, and their future perspectives as promising bioapplicable materials.
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http://dx.doi.org/10.1039/d1cs00804hDOI Listing
January 2022

Pyridinium-conjugated polynorbornenes for nanomolar ATP sensing using an indicator displacement assay and a PET strategy.

Chem Commun (Camb) 2021 Dec 14;57(99):13530-13533. Epub 2021 Dec 14.

Department of Chemistry, Korea University, Seoul 02841, Korea.

An indicator displacement assay, namely polymeric PNPY-n/UD consisting of a cationic polynorbornene backbone with pyridinium functional groups (PNPY-1,2,3) and an anionic uranine dye (UD) as an indicator, has been developed for highly sensitive "turn-on" fluorescence sensing of ATP. While PNPY-1/UD itself is non-emissive, a bright green fluorescence signal was observed in the presence of ATP [ = 2.17 × 10 M, LOD = 5.7 nM]. The potential of a highly photostable system PNPY-1/UD was also validated in detecting ATP levels in live-cell imaging applications.
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http://dx.doi.org/10.1039/d1cc05500cDOI Listing
December 2021

Septal deviation could be associated with the development of bronchial asthma: A nationwide cohort study.

J Allergy Clin Immunol Pract 2022 04 12;10(4):1099-1101.e1. Epub 2021 Nov 12.

Research Institute of Clinical Medicine of Jeonbuk, National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea; Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Medical School, Jeonju, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2021.11.002DOI Listing
April 2022

Calix[]triazolium based turn-on fluorescent sensing ensemble for selective adenosine monophosphate (AMP) detection.

Chem Commun (Camb) 2021 Nov 16;57(91):12139-12142. Epub 2021 Nov 16.

College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.

A novel calix[]triazolium was synthesized and exhibited excellent selectivity for AMP. The binding between calix[]triazolium and chromenolate anions forms a non-fluorescent complex and the resulting supramolecular ensemble selectively detects AMP in water and induces "turn-on" fluorescence. The sensing platform is the first macrocyclic system to discriminate AMP from ADP and ATP through fluorescence changes.
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http://dx.doi.org/10.1039/d1cc04950jDOI Listing
November 2021
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