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Kim, Inhye,Song, Young Ho,Singh, Nem,Jeong, Yong Joon,Kwon, Jung Eun,Kim, Hyunuk,Cho, Young Mi,Kang, Se Chan,Chi, Ki-Whan Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.specal
<P>Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3, 6-bis(pyridin-3- ylethynyl) phenanthrene (bpep) (<B>1</B>) and one of the three dinuclear arene ruthenium clips, [(η6-<I>p</I>-iPrC<SUB>6</SUB>H<SUB>4</SUB>Me)<SUB>2</SUB>Ru<SUB>2</SUB>-(OO\OO)][OTf]<SUB>2</SUB> (OO\OO =2, 5-dioxido-1, 4-benzoquinonato, OTf = triflate) (<B>2</B>), 5, 8-dioxido-1, 4-naphthoquinonato (<B>3</B>), or 6, 11-dioxido-5, 12-naphthacenediona (<B>4</B>), resulted in three molecular bowls <B>5</B>–<B>7</B> of general formula [{(η6-<I>p</I>-iPrC<SUB>6</SUB>H<SUB>4</SUB>Me)<SUB>2</SUB>Ru<SUB>2</SUB>-(OO\OO)}<SUB>2</SUB>(bpep)<SUB>2</SUB>][OTf]<SUB>4</SUB>. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization–mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl <B>5</B> was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls <B>5</B>–<B>7</B> were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl <B>6</B> showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl <B>6</B>. Bowl <B>6</B> also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl <B>6</B> promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl <B>6</B> induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl <B>6</B> is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study.</P>
Kim, Inhye,Jeong, Heon-Ho,Kim, Yong-Jae,Lee, Na-Eun,Huh, Kang-moo,Lee, Chang-Soo,Kim, Geon Hee,Lee, Eunji The Royal Society of Chemistry 2014 Journal of Materials Chemistry B Vol.2 No.38
<P>We prepared pyrene-labeled peptide amphiphiles (PAs) consisting of a hydrophobic linear- or branched-alkyl chain (for 1 or 2, respectively) and a hydrophilic histidine-rich peptide of HGGGHGHGGGHG (HG12). Both peptides have a strong tendency to form nanofibrils (NFs) in aqueous media. The resulting histidine-coated NFs show a great binding affinity to Cu<SUP>2+</SUP> as a fluorescence “light-off” sensor. Interestingly, the emission spectra of the pyrene probe show that the different supramolecular assemblies between 1 and 2 can significantly affect the binding affinity to specific metal ions. In particular, “light-up” fluorescent Ag<SUP>+</SUP> detection of NFs of 2 through inhibition of photoinduced electron transfer (PET) was observed even at a low concentration of PA solution. As a means to determine the biological responsibility of 2 to Ag<SUP>+</SUP>, intracellular detection using the “turn-on” response was performed. A considerable enhancement of fluorescence in NF-loaded HeLa cells was observed. In addition, the NFs were used as a template scaffold for the production of Ag nanoparticles (AgNPs) with high monodispersity and stability. The NFs decorated with AgNPs are shown to possess highly effective and long-term antibacterial activity against both Gram-negative and -positive bacteria.</P>
Kim, Youngjin,Kim, Inhye,Lee, Taek Seung,Lee, Eunji,Lee, Kyung Jin Elsevier 2018 Journal of industrial and engineering chemistry Vol.60 No.-
<P><B>Abstract</B></P> <P>Cesium adsorbent was fabricated by synthesizing Prussian blue (PB) via redox reaction between K<SUB>3</SUB>[Fe(CN)<SUB>6</SUB>] and FeCl<SUB>3</SUB> in inverse-high-internal-phase-emulsion (i-HIPE) hydrogel. The PB nanoparticles are successfully generated via novel pathway, in-situ redox reaction in hydrogel. Maximum cesium ion uptake capacity of composite is 0.1047mmol/g (per composite amount) which is 3-times higher than that of purchased PB, even though very small amount of PB have been inserted. Adsorption kinetics and isotherm of PB/i-HIPE hydrogel was followed to pseudo-first-order and Langmuir model respectively. These results can provide excellent pathway to design effective absorbent for removal of radio-active, aqueous cesium ion in environments.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Prussian blue nanoparticles were synthesized by a redox reaction in the porous hydrogel. </LI> <LI> PB nanoparticles were dispersed homogeneously in i-HIPE hydrogel. </LI> <LI> Fabricated adsorbent followed pseudo-first-order kinetics and Langmuir isotherm. </LI> <LI> Hydrogel-based adsorbent has efficient cesium uptake abilities in many conditions. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Prussian blue nanoparticles were synthesized in the porous hydrogel by a redox reaction for effective adsorption of Cs ion in aqueous condition. The results of cesium uptake test showed that PB-containing i-HIPE hydrogel has higher and efficient cesium uptake ability compared to previous works owing to homogeneous and well-dispersion of PB particle in porous hydrogel.</P> <P>[DISPLAY OMISSION]</P>
Kim, Inhye,Han, Eun Hee,Ryu, Jooyeon,Min, Jin-Young,Ahn, Hyungju,Chung, Young-Ho,Lee, Eunji American Chemical Society 2016 Biomacromolecules Vol.17 No.10
<P>We report a simple and facile strategy for the preparation of multifunctional nanoparticles with programmable properties using self assembly of precisely designed block amphiphiles in an aqueous solution state. Versatile, supramolecular nanoplatform for personalized needs, particularly-theranostics, was fabricated by coassembly of peptide amphiphiles (PAs) in aqueous solution, replacing time-consuming and inaccessible chemical synthesis. Fibrils, driven by the assembly of hydrophobic beta-sheet forming peptide block, were utilized as a nano template for drug loading within their robust core. PAs were tagged with octreotide [somatostatin (SST) analogue] for tumor-targeting or were conjugated with paramagnetic metal ion (Gd3+)-chelating 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for magnetic resonance (MR) imaging. The two PA types were coassembled to integrate each PA function into original fibrillar nanotemplates. The adoption of a bulky target-specific cyclic octreotide and beta-sheet-forming peptide with enhanced hydrophobicity led morphological transition from conventional fibrils to helical fibrils. The resulting one-dimensional nanoaggregates allowed the successful intracellular delivery of doxorubicin (DOX) to MCF-7 cancer cells overexpressing SST receptor (SSTR) and MR imaging by enabling high longitudinal (T-1) relaxivity of water protons. Correlation between the structural nature of fibrils formed by PA coassembly and contrast efficacy was elucidated. The coassembly of PAs with desirable functions may thus be a useful strategy for the generation of tailor-made biocompatible nanomaterials.</P>
Structure-Dependent Antimicrobial Theranostic Functions of Self-Assembled Short Peptide Nanoagents
Kim, Inhye,Jin, Seon-Mi,Han, Eun Hee,Ko, Eunhee,Ahn, MiJa,Bang, Woo-Young,Bang, Jeong-Kyu,Lee, Eunji American Chemical Society 2017 Biomacromolecules Vol.18 No.11
<P>Gadolinium (Gd[III])-based nanoaggregates are potential noninvasive magnetic resonance imaging (MRI) probes with excellent spatial and temporal resolution for cancer diagnosis. Peptides conjugated with Gd<SUP>3+</SUP> can aid in supramolecular scaffolding for MRI nanoagents because of their inherent biocompatibility and degradability. We report here a strategy to tune the MR relaxivity of tumor cell-targeted nanoagents and enhance the antimicrobial and anticancer activities of nanoagents based on rationally designed antimicrobial peptide (AMP) assembly. A tripeptide with glycyl-<SMALL>l</SMALL>-histidyl-<SMALL>l</SMALL>-lysine (GHK) capable of Gd<SUP>3+</SUP> chelation was attached to short AMPs containing pyrazole amino acids that spontaneously assembled as a function of the number of hydrophobic amino acid residues and the peptide length of AMPs. Aqueous coassembly of GHK with tumor-targeting, cyclic arginine-glycine-aspartic acid (cRGD)-tagged AMPs resulted in the formation of micelles, fibrils, vesicles, sheets, and planar networks. Interestingly, the two-dimensional planar network nanostructure showed less antibacterial activity and tumor cell cytotoxicity but greater drug loading/delivery and magnetic resonance signaling than micelles because of its intrinsic structural characteristics. This study can provide a rational approach for the design and fabrication of clinically useful nanoagents.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2017/bomaf6.2017.18.issue-11/acs.biomac.7b00951/production/images/medium/bm-2017-00951h_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bm7b00951'>ACS Electronic Supporting Info</A></P>
Casein Kinase 2 Inhibitor, CX-4945, as a Potential Targeted Anticancer Agent in Gastric Cancer
KIM, HYUN MYONG,JEONG, INHYE,KIM, HYUN JEONG,KANG, SUN KYOUNG,KWON, WOO SUN,KIM, TAE SOO,PARK, KYU HYUN,JUNG, MINKYU,SOONG, JOHN,LIN, SHU-CHUAN,CHUNG, HYUN CHEOL,RHA, SUN YOUNG Anticancer Research USA Inc. 2018 Anticancer research Vol.38 No.11