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Lee, Si Yeon,Lee, Sangmin,Lee, Jangwook,Yhee, Ji Young,Yoon, Hwa In,Park, Soon-Jung,Koo, Heebeom,Moon, Sung-Hwan,Lee, Hyukjin,Cho, Yong Woo,Kang, Sun Woong,Lee, Sang-Yup,Kim, Kwangmeyung Elsevier 2016 Biochemical and biophysical research communication Vol.479 No.4
<P><B>Abstract</B></P> <P>Labeling of stem cells aims to distinguish transplanted cells from host cells, understand <I>in vivo</I> fate of transplanted cells, particularly important in stem cell therapy. Adipose-derived mesenchymal stem cells (ASCs) are considered as an emerging therapeutic option for tissue regeneration, but much remains to be understood regarding the <I>in vivo</I> evidence. In this study, a simple and efficient cell labeling method for labeling and tracking of stem cells was developed based on bio-orthogonal copper-free click chemistry, and it was applied in a mouse hindlimb ischemia model. The human ASCs were treated with tetra-acetylated <I>N</I>-azidoacetyl-<SMALL>D</SMALL>-mannosamine (Ac<SUB>4</SUB>ManNAz) to generate glycoprotein with unnatural azide groups on the cell surface, and the generated azide groups were fluorescently labeled by specific binding of dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5). The safe and long-term labeling of the hASCs by this method was first investigated <I>in vitro</I>. Then the DBCO-Cy5-hASCs were transplanted into the hindlimb ischemia mice model, and we could monitor and track <I>in vivo</I> fate of the cells using optical imaging system. We could clearly observe the migration potent of the hASCs toward the ischemic lesion. This approach to design and tailor new method for labeling of stem cells may be useful to provide better understanding on the therapeutic effects of transplanted stem cells into the target diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A new method was proposed for labeling and tracking of stem cells. </LI> <LI> This method enables safe and long-term monitoring of stem cells <I>in vivo</I>. </LI> <LI> We observed the migration of the stem cells toward the ischemic lesion. </LI> </UL> </P>
Lee, Hyukjin,Ahn, Cheol-Hee,Park, Tae Gwan WILEY-VCH Verlag 2009 Macromolecular bioscience Vol.9 No.4
<P>PLGA-grafted HA copolymers were synthesized and utilized as target specific micelle carriers for DOX. For grafting hydrophobic PLGA chains onto the backbone of hydrophilic HA, HA was solubilized in an anhydrous DMSO by nano-complexing with dimethoxy-PEG. The carboxylic groups of HA were chemically grafted with PLGA, producing HA-g-PLGA copolymers. Resultant HA-g-PLGA self-assembled in aqueous solution to form multi-cored micellar aggregates and DOX was encapsulated during the self-assembly. DOX-loaded HA-g-PLGA micelle nanoparticles exhibited higher cellular uptake and greater cytotoxicity than free DOX for HCT-116 cells that over-expressed HA receptor, suggesting that they were taken up by the cells via HA receptor-mediated endocytosis.</P><P> <img src='wiley_img/16165187-2009-9-4-MABI200800229-gra001.gif' alt='wiley_img/16165187-2009-9-4-MABI200800229-gra001'> </P>
Development of RNA therapeutics and lipid nanoparticle (LNP) formulation for in vivo delivery
Hyukjin LEE 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10
In recent years, RNA therapeutics have received tremendous attention as a tool to regulate gene expression in patients. These approaches include the regulation of abnormal gene expression by short interfering RNA (siRNA) and messenger RNA (mRNA). There have been two US FDA approved siRNA therapeutics (Patisiran and Givosiran) for rare disease treatments. These drugs target the selective degradation of mRNA to reduce the expression of disease associated proteins in polyneuropathy and acute hepatic porphyria. In addition, synthetic mRNA can produce insufficient proteins (e.g. Factor IX, VEGF) in patients to treat various diseases such as hemophilia A and ischemic heart disease. To fully realize the potential of RNA therapeutics, an efficient in vivo delivery system is of the utmost importance. Ionizable lipid nanoparticles (LNPs) have been widely utilized for the systemic delivery of RNA therapeutics. LNPs are mainly composed of ionizable lipid or lipid like materials with helper lipid, cholesterol, and polyethylene glycol (PEG)-lipid. Although LNPs are particularly advantageous for in vivo delivery, systemic delivery of RNA therapeutics other than liver hepatocytes remains highly challenging. Ionizable lipid nanoparticles (LNPs) have been widely utilized for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol (PEG)-lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE mediated cellular uptake through LDL receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type specific delivery of RNA into the liver and other tissues.
Lee Hak-Dong,Paje Leo Adrianne,Lee Sullim,Kang Ki Sung,Hong Kyungki,Kwon Hyukjin,Lee Sanghyun 한국응용생명화학회 2021 Applied Biological Chemistry (Appl Biol Chem) Vol.64 No.S
An analytical method was established to identify and quantify hydroxycinnamic acids, such as 1,5-dicaffeoylquinic acid (DCQA) and chicoric acid (CA), in mixtures of Saussurea grandifolia and Taraxacum coreanum (MST) by using reverse-phase high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Analyses were carried out by using an INNO C18 column with a gradient elution system, and different parameters were used to validate our optimized method. Results demonstrated limits of detection and quantification of 5.46 × 10– 3 and 16.54 × 10– 3 mg/mL for DCQA and 0.37 × 10– 3 and 1.14 × 10– 3 mg/mL for CA, respectively. The calibration curves for DCQA and CA showed good linearity over the concentration ranges of 0.025–0.4 and 0.00625–0.1 mg/mL, respectively, and both exhibited r2 = 1.0000. In the accuracy test, high recovery rates were obtained ranging from 101.16–104.18% for DCQA and 97.55–108.49% for CA, while the precision values were ≤ 1.00% for DCQA and ≤ 1.21% for CA. The values obtained from our analyses support the use of this analytical method for the accurate identification and quantification of DCQA and CA from MST. Our methodology could be used further to determine the content of hydroxycinnamic acid derivatives in routine analyses and large-scale extraction processes.
Lee, Hee Suk,Lee, Jeongyup,Yoon, Byengsuk,Yim, Youjin,Choi, Ilhwan,Cho, Hyukjin,Lee, Songhee,Baik, Kyounghee,Park, Ju Hyeon,Huh, Yu Jeong IWA Publishing 2013 WATER SCIENCE AND TECHNOLOGY -WATER SUPPLY- Vol.13 No.5
<P>Due to the tragic disaster that happened in Japan and crippled the Fukushima nuclear power plant, serious concerns have been raised regarding the contamination of drinking water as a result of the radioactive materials that were released. Even though the quantities of radioactive material in rain were relatively low, people were concerned about the drinking water. Therefore, there is a need to know the removal efficiency of the unit process of water treatment and to prepare a safety plan to protect the public's health from radioactive materials. In this study, the laboratory scale removal rates were estimated for the coagulation/flocculation, adsorption, and ion exchange processes. The reference standard materials which are stable elements, Cesium-133 (Cs-133) and Iodine-127 (I-127), were used for the typical and advanced water treatment processes at the laboratory scale. For the coagulation/flocculation process, three major coagulants were assessed for this process. However, the removal rates of this process were low. For the adsorption process, powdered activated carbon and zeolites were investigated. The powdered activated carbon showed insignificant removal rates for both reference materials. However, synthetic zeolite was an effective process for Cs-133, and the ion exchange method showed high removal rates for both Cs-133 and I-127.</P>
Lee, So Yeong,Kim, Sung Han,Kim, Sung Min,Lee, Hyukjin,Lee, Gibaek,Park, Sung Young The Royal Society of Chemistry 2014 NEW JOURNAL OF CHEMISTRY Vol.38 No.6
<P>A novel type of zwitterionic fluorescent nanoparticles (ZFNPs) containing polysulfobetaine groups, the boron dipyrromethane (BODIPY) fluorophore and graphene oxide plates is prepared for the detection of tumor cells in response to the intra- and extracellular stimuli. The fluorescence intensities of the ZFNPs are highly influenced by temperature and pH.</P> <P>Graphic Abstract</P><P>Novel fluorescence probes, reduced graphene oxide (rGO) containing zwitterionic fluorescent nanoparticles, for effective diagnosis of cancer cells. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3nj01641b'> </P>