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Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song Suah Yang Jinseong Kim Yujeong Moon Nayeon shim Hong Yeol Yoon Sehoon Kim Man kyu shim Kwangmeyung Kim KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

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Cathepsin B-responsive prodrugs for cancer-targeted therapy:Recent advances and progress for clinical translation

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Nano Research 2022年第8期15卷 7247-7266页

作者： Seong Ik Jeon Suah Yang Man kyu shim Kwangmeyung Kim Biomedical Research Institute Korea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea

The cathepsin B-responsive prodrugs are promising strategies to reduce the serious adverse effects of anticancer drugs by improving the cancer selectivity that can be specifically activated by overexpressed cathepsin B in targeted cancer ***,clinical translation of such therapeutic approaches has been restricted by low antitumor efficacy that is mainly attributable to undesirable pharmacokinetic profiles and inefficient tumor-targeting of cathepsin B-responsive prodrugs,due to their small-molecule *** recent decades,many researchers have widely investigated the drug delivery system(DDS)to improve the in vivo pharmacokinetic profiles and tumor-targeting efficiency of cathepsin B-responsive prodrugs via the application of polymers,dendrimers,antibodies,lipids,and inorganic nanoparticles as drug *** addition,the potential therapeutic efficacy of DDS for cathepsin B-responsive prodrugs is demonstrated in multiple studies and combinatorial treatment with typical therapeutic modalities can effectively overcome the challenges of tumor heterogeneity and multidrug *** this review,recent advances and progress of new DDS for cathepsin B-responsive prodrugs are outlined,and their clinical trials are ***,potential challenges and the outlooks for clinical translation of cathepsin B-responsive prodrugs are highlighted.

关键词： cathepsin B prodrug chemotherapy drug delivery system targeted cancer therapy

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Dynamic changes of protein corona compositions on the surface of zinc oxide nanoparticle in cell culture media

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Frontiers of Chemical Science and Engineering 2019年第1期13卷 90-97页

作者： Vo-Van Giau Yoon-Hee Park kyu-Hwan shim Sang-Wook Son Seong-Soo A. An Department of Bionanotechnology and Gachon Medical Research Institute Gachon University and Gachon Medical Research Institute Seongnam Korea Laboratory of Cell Signaling and Nanomedicine Department of Dermatology and Division of Brain Korea 21 Project for Biomedical Science Korea University College of Medicine Seoul Korea

The potential applications of nanomaterials used in nanomedicine as ingredients in drug delivery systems and in other products continue to expand. When nanomaterials are introduced into physiological environments and driven by energetics, they readily associate proteins forming a protein corona (PC) on their surface. This PC could result in an alteration of the nanomatcrial's surface characteristics, affecting their interaction with cells due to conformational changes in adsorbed protein molecules. However, our current understanding of nanobiological interactions is still very limited. Utilizing a liquid chromatography-mass spectroscopy/mass spectroscopy technology and a Cytoscape plugin (ClueGO) approach, we examined the composition of the PC for a set of zinc oxide nanoparticles (ZnONP) from cell culture media typically and further analyzed the biological interaction of identified proteins, respectively. In total, 36 and 33 common proteins were investigated as being bound to ZnONP at 5 min and 60 min, respectively. These proteins were further analyzed with ClueGO, a Cytoscape plugin, which provided gene ontology and the biological interaction processes of identified proteins. Proteins bound to the surface of nanoparticles that may modify the structure, therefore the function of the adsorbed protein could be consequently affect the complicated biological processes.

关键词： ZnONPs nanoparticles protein corona ClueGO

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Boosting Pseudocapacitive Behavior of Supercapattery Electrodes by Incorporating a Schottky Junction for Ultrahigh Energy Density

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Nano-Micro Letters 2023年第5期15卷 15-35页

作者： Selvaraj Seenivasan kyu in shim Chaesung Lim Thangavel Kavinkumar Amarnath T.Sivagurunathan Jeong Woo Han Do-Heyoung Kim School of Chemical Engineering Chonnam National University77 Yongbong-RoGwangju 61186Republic of Korea Division of Environmental Science and Engineering Pohang University of Science and Technology(POSTECH)Pohang 37673Republic of Korea Department of Chemical Engineering Pohang University of Science and Technology(POSTECH)Pohang 37673Republic of Korea

Pseudo-capacitive negative electrodes remain a major bottleneck in the development of supercapacitor devices with high energy density because the electric double-layer capacitance of the negative electrodes does not match the pseudocapacitance of the corresponding positive *** the present study,a strategically improved Ni-Co-Mo sulfide is demonstrated to be a promising candidate for high energy density supercapattery devices due to its sustained pseudocapacitive charge storage *** pseudocapacitive behavior is enhanced when operating under a high current through the addition of a classical Schottky junction next to the electrode-electrolyte interface using atomic layer *** Schottky junction accelerates and decelerates the diffusion of OH-/K+ions during the charging and discharging processes,respectively,to improve the pseudocapacitive *** resulting pseudocapacitive negative electrodes exhibits a specific capacity of 2,114 C g^(-1)at 2 A g^(-1)matches almost that of the positive electrode’s 2,795 C g^(-1)at 3 A g^(-1).As a result,with the equivalent contribution from the positive and negative electrodes,an energy density of 236.1 Wh kg^(-1)is achieved at a power density of 921.9 W kg^(-1)with a total active mass of 15 mg *** strategy demonstrates the possibility of producing supercapacitors that adapt well to the supercapattery zone of a Ragone plot and that are equal to batteries in terms of energy density,thus,offering a route for further advances in electrochemical energy storage and conversion processes.

关键词： Pseudo-capacitance Negative electrode Supercapattery Atomic layer deposition Energy density

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Beauty of the beast: anticholinergic tropane alkaloids in therapeutics

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Natural Products and Bioprospecting 2022年第1期12卷 515-529页

作者： kyu Hwan shim Min Ju Kang Niti Sharma Seong Soo A.An Bionano Research Institute Gachon University1342 Seongnam-daeroSujeong-GuSeongnam 461-701South Korea Department of Neurology Veterans Health Service Medical CenterVeterans Medical Research InstituteSeoulSouth Korea

Tropane alkaloids(TAs)are among the most valued chemical compounds known since pre-historic *** plants from Solanaceae family(Hyoscyamus niger,Datura,Atropa belladonna,Scopolia lurida,Mandragora officinarum,Duboisia)and Erythroxylaceae(Erythroxylum coca)are rich sources of tropane *** compounds possess the anticholinergic properties as they could block the neurotransmitter acetylcholine action in the central and peripheral nervous system by binding at either muscarinic and/or nicotinic ***,they are of great clinical impor-tance and are used as antiemetics,anesthetics,antispasmodics,bronchodilator and *** also serve as the lead compounds to generate more effective *** to the important pharmacological action they are listed in the WHO list of essential medicines and are available in market with FDA ***,being anticholinergic in action,TA medication are under the suspicion of causing dementia and cognitive decline like other medications with anticholinergic action,interestingly which is *** are published reviews on chemistry,biosynthesis,phar-macology,safety concerns,biotechnological aspects of TAs but the detailed information on anticholinergic mecha-nism of action,clinical pharmacology,FDA approval and anticholinergic burden is *** the present review tries to fill this lacuna by critically summarizing and discussing the above mentioned aspects.

关键词： Tropane alkaloids Poisonous plants Anticholinergic action Muscarinic and nicotinic receptors Therapeutics Anticholinergic burden

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All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy

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Bioactive Materials 2023年第10期28卷 358-375页

作者： Sukyung Song Man kyu shim Suah Yang Jaewan Lee Wan Su Yun Hanhee Cho Yujeong Moon Jin Young Min Eun Hee Han Hong Yeol Yoon Kwangmeyung Kim College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul03760Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul02792Republic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul02841Republic of Korea Department of Bioengineering Korea UniversitySeoul02841Republic of Korea Research Center for Bioconvergence Analysis Korea Basic Science Institute(KBSI)Cheongju28119Republic of Korea Department of Toxicology College of PharmacyChungnam National UniversityDaejeon34134Republic of Korea

Synergistic immunotherapy of immune checkpoint blockade (ICB) and immunogenic cell death (ICD) has shown remarkable therapeutic efficacy in various cancers. However, patients show low response rates and undesirable outcomes to these combination therapies owing to the recycling mechanism of programmed death-ligand 1 (PD-L1) and the systemic toxicity of ICD-inducing chemotherapeutic drugs. Herein, we propose all-in-one glycol chitosan nanoparticles (CNPs) that can deliver anti-PD-L1 peptide (PP) and doxorubicin (DOX) to targeted tumor tissues for a safe and more effective synergistic immunotherapy. The PP-CNPs, which are prepared by conjugating ᴅ-form PP (NYSKPTDRQYHF) to CNPs, form stable nanoparticles that promote multivalent binding with PD-L1 proteins on the targeted tumor cell surface, resulting in effective lysosomal PD-L1 degradation in contrast with anti-PD-L1 antibody, which induces recycling of endocytosed PD-L1. Consequently, PP-CNPs prevent subcellular PD-L1 recycling and eventually destruct immune escape mechanism in CT26 colon tumor-bearing mice. Moreover, the ICD inducer, DOX is loaded into PP-CNPs (DOX-PP-CNPs) for synergistic ICD and ICB therapy, inducing a large number of damage-associated molecular patterns (DAMPs) in targeted tumor tissues with minimal toxicity in normal tissues. When the DOX-PP-CNPs are intravenously injected into CT26 colon tumor-bearing mice, PP and DOX are efficiently delivered to the tumor tissues via nanoparticle-derived passive and active targeting, which eventually induce both lysosomal PD-L1 degradation and substantial ICD, resulting in a high rate of complete tumor regression (CR: 60%) by a strong antitumor immune response. Collectively, this study demonstrates the superior efficacy of synergistic immunotherapy using all-in-one nanoparticles to deliver PP and DOX to targeted tumor tissues.

关键词： Chitosan nanoparticle Synergistic immunotherapy Immune checkpoint blockade Multivalent binding Immunogenic cell death

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Mixed-dimensional stacked nanocomposite structures for a specific wavelength-selectable ambipolar photoresponse

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Nano Research 2024年第6期17卷 5549-5558页

作者： Young Jae Park Jaeho shim Joo Song Lee kyu Seung Lee Ji-Yeon Kim Kang Bok Ko Sang-Youp Yim Seongjun Kim Hoon-kyu Shin Donghee Park Yong Ju Yun Dong Ick Son Institute of Advanced Composite Materials Korea Institute of Science and TechnologyJeollabuk-do 55324Republic of Korea National Institute for Nanomaterials Technology Pohang University of Science and TechnologyGyeongsangbuk-do 37673Republic of Korea Department of Semiconductor Science and Technology Semiconductor Physics Research CenterJeonbuk National UniversityJeonju 54896Republic of Korea Advanced Photonics Research Institute Gwangju Institute of Science and TechnologyGwangju 61005Republic of Korea Center for Opto-Electronic Materials and Devices Post-Silicon Semiconductor InstituteKorea Institute of Science and TechnologySeoul 02792Republic of Korea Graduate School of Energy and Environment(KU-KIST Green School) Korea UniversitySeoul 02841Republic of Korea KIST School Department of Nanomaterials and Nano ScienceUniversity of Science and Technology(UST)Daejeon 34113Republic of Korea

Mixed-dimensional composite structures using zero-dimensional(0D)quantum dots(QDs)and two-dimensional(2D)transition metal dichalcogenides(TMDs)materials are expected to attract great interest in optoelectronics due to the potential to generate new optical ***,we report on the unique optical characteristics of a devices with mixed dimensional vertically stacked structures based on tungsten diselenide(WSe_(2))/CdSeS QDs monolayer/molybdenum disulfide(MoS_(2))(2D/0D/2D).Specifically,it exhibits an ambipolar photoresponse characteristic,with a negative photoresponse observed in the 400-600 nm wavelength range and a positive photoresponse appeared at 700 nm *** resulted in the high negative responsivity of up to 52.22 mA·W^(−1)under 400 nm,which is 163 times higher than that of the photodetector without CdSeS *** also demonstrated the negative photoresponse,which could be due to increased carrier collision probability and non-radiative *** modeling and simulation reveal that Auger recombination among the types of non-radiative recombination is the main cause of negative photocurrent ***,we discovered ambipolar photoresponse near a specific wavelength corresponding to the energy of quantum *** study revealed interesting phenomenon in the mixed low-dimensional stacked structure and paved the way to exploit it for the development of innovative photodetection materials as well as for optoelectronic applications.

关键词： mixed-dimension quantum dot heterostructure photodetector ambipolar photoresponse

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Hepatocellular carcinoma with macrovascular invasion:need a personalized medicine for this complicated event

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 188-190页

作者： Hyeonseung Hwang Ju Hyun shim Jin Hyoung Kim Department of Radiology and Research Institute of Radiology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Department of Gastroenterology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea

Hepatocellular carcinoma(HCC)is a hypervascular tumor and has a tendency to invade portal vein(PV)or hepatic vein(HV).HCC with macrovascular invasion(MVI)is associated with poor prognosis(1).HCC invasion of PV can lead to rapid intrahepatic tumor *** addition,portal vein tumor thrombus(PVTT)may result in deterioration of hepatic function,as well as increased risk of portal hypertensive complications(2).HCC invasion of HV is associated with increased risk of systemic ***.

关键词： invasion hepatic hypertensive

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Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

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Marine Life Science & Technology 2024年第1期6卷 84-92页

作者： Yuna Jung Chaesun Kwon Taeyeon Kim Jin Woo Lee Min-Kyoo Shin Sang Hee shim Natural Products Research Institute College of PharmacySeoul National UniversitySeoul 08826Republic of Korea College of Pharmacy and Research Institute of Pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea College of Pharmacy Duksung Women’s UniversitySeoul 01369Republic of Korea

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing structures and biological *** the present study,two new tetramic acid alkaloids tolypyridone I(1)and tolypyridone J(2),together with five known ones(3–7),were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North *** structures were elucidated using 1D,2D NMR,and *** configurations were established on the basis of 1H coupling constants,ROESY correlations and DP4 *** 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane,hindering *** our unbiased screening to discover neuroprotective compounds in an in vitro Parkinson’s disease(PD)model,SH-SY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium(MPP^(+)),a parkinsonian *** tested compounds,F-14329(7)significantly protected cells from MPP^(+)-induced ***^(+)-mediated cell death is known to be related to the regulation of Bcl-2 family proteins,specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax *** with 2 mmol/L of MPP^(+)for 24 h significantly reduced Bcl-2 levels compared to control treated with ***,treatment with F-14329(7)attenuated such *** study demonstrates that tetramic acid-motif compounds could be potential lead compounds for treating PD.

关键词： Tolypocladium cylindrosporum Tetramic acid Tolypyridone Parkinson’s disease

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The PRR-EC complex and SWR1 chromatin remodeling complex function cooperatively to repress nighttime hypocotyl elongation by modulating PIF4 expression in Arabidopsis

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Plant Communications 2024年第9期5卷 184-199页

作者： Jin Hoon Won Jeonghyang Park Hong Gil Lee Sangrae shim Hongwoo Lee Eunkyoo Oh Pil Joon Seo Department of Chemistry Seoul National UniversitySeoul 08826Republic of Korea Department of Life Sciences Korea UniversitySeoul 02841Republic of Korea Plant Genomics and Breeding Institute Seoul National UniversitySeoul 08826Republic of Korea Department of Forest Resources Kangwon National UniversityChuncheon 24341Republic of Korea

The circadian clock entrained by environmental light-dark cycles enables plants to fine-tune diurnal growth and developmental ***,we show that physical interactions among evening clock components,including PSEUDO-RESPONSE REGULATOR 5(PRR5),TIMING OF CAB EXPRESSION 1(TOC1),and the Evening Complex(EC)component EARLY FLOWERING 3(ELF3),define a diurnal repressive chromatin structure specifically at the PHYTOCHROME-INTERACTING FACTOR 4(PIF4)locus in *** three clock components act interdependently as well as independently to repress nighttime hypocotyl elongation,as hypocotyl elongation rate dramatically increased specifically at nighttime in the prr5-1 toc1-21 elf3-1 mutant,concomitantly with a substantial increase in PIF4 *** repression of PIF4 by ELF3,PRR5,and TOC1 is mediated by the SWI2/SNF2-RELATED(SWR1)chromatin remodeling complex,which incorporates histone H2A.Z at thePIF4 locus,facilitating robust epigenetic suppression ofPIF4 during the ***,these findings demonstrate that the PRR-EC-SWR1 complex represses hypocotyl elongation at night through a distinctive chromatin domain covering PIF4 chromatin.

关键词： hypocotyl elongation circadian clock PRR Evening Complex histone H2A.Z SWR1 complex

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