568 research outputs found
The effective nuclear delivery of doxorubicin from dextran-coated gold nanoparticles larger than nuclear pores
No full textTo date, gold nanoparticles (AuNPs) have been investigated for diverse bioapplications. Generally, AuNPs are engineered to possess surface coating with organic/inorganic shells to increase colloidal stability in biological solutions and to facilitate chemical conjugation. In the present study, we developed a strategy to prepare dextran-coated AuNPs with control over its size by simply boiling an aqueous solution of Au salt and dextran, in which dextran serves as both reducing agent for AuNP (Au(0)) formation from Au(III) and AuNP surface coating material. The prepared dextran-coated AuNPs (dAuNPs) maintained its colloidal stability under high temperature, high salt concentration, and extreme pH. Importantly, the dAuNP remarkably improved efficacy of an anti-cancer agent, doxorubicin (Dox), when harnessed as a Dox delivery carrier. The half-maximal inhibitory concentration (EC50) of Dox-conjugated dAuNP with diameter of 170 nm was w9 pM in HeLa cells, which was 1.1 105 times lower than that of free Dox and lower than any previously reported values of Dox-nanoparticle complex. Interestingly, smaller AuNPs with 30 and 70 nm showed about 10 times higher EC50 than 170 nm AuNPs when treated to HeLa cells after conjugation with Dox. To achieve high cytotoxicity as cancer therapeutics, Dox should be delivered into nucleus to intercalate with DNA double helix. We show here that Dox-AuNPs was far more efficient as an anti-cancer drug than free Dox by releasing from AuNPs through spontaneous degradation of dextran, allowing free diffusion and nuclear uptake of Dox. We also revealed that larger AuNPs with lower degree of dextran crosslinking promoted faster degradation of dextran shells.148541sciescopu
High-throughput chemical screening to discover new modulators of microRNA expression in living cells by using graphene-based biosensor
No full textMicroRNAs (miRNAs) are important regulatory RNAs that control gene expression in various biological processes. Therefore, control over the disease-related miRNA expression is important both for basic research and for a new class of therapeutic modality to treat serious diseases such as cancer. Here, we present a high-throughput screening strategy to identify small molecules that modulate miRNA expression in living cells. The screen enables simultaneous monitoring of the phenotypic cellular changes associated with the miRNA expression by measuring quantitative fluorescent signals corresponding to target miRNA level in living cells based on a novel biosensor composed of peptide nucleic acid and nano-sized graphene oxide. In this study, the biosensor based cellular screening of 967 compounds (including FDA-approved drugs, enzyme inhibitors, agonists, and antagonists) in cells identified four different classes of small molecules consisting of (i) 70 compounds that suppress both miRNA-21 (miR-21) expression and cell proliferation, (ii) 65 compounds that enhance miR-21 expression and reduce cell proliferation, (iii) 2 compounds that suppress miR-21 expression and increase cell proliferation, and (iv) 21 compounds that enhance both miR-21 expression and cell proliferation. We further investigated the hit compounds to correlate cell morphology changes and cell migration ability with decreased expression of miR-21 © Te Author(s) 201
Highly Biocompatible Carbon Nanodots for Simultaneous Bioimaging and Targeted Photodynamic Therapy In Vitro and In Vivo
No full textPhotosensitizers (PSs) are light-sensitive molecules that are highly hydrophobic, which poses a challenge to their use for targeted photodynamic therapy. Hence, considerable efforts have been made to develop carriers for the delivery of PSs. Herein, a novel design is described of highly biocompatible, fluorescent, folic acid (FA)-functionalized carbon nanodots (CDs) as carriers for the PS zinc phthalocyanine (ZnPc) to achieve simultaneous biological imaging and targeted photodynamic therapy. FA is modified on PEG--passivated CDs (CD-PEG) for targeted delivery to FA-positive cancer cells, and ZnPc is loaded onto CD-PEG-FA via ??-?? stacking interactions. CD-PEG-FA/ZnPc exhibits excellent targeted delivery of the PS, leading to simultaneous imaging and significant targeted photodynamic therapy after irradiation in vitro and in vivo. The present CD-based targeted delivery of PSs is anticipated to offer a convenient and effective platform for enhanced photodynamic therapy to treat cancers in the near future.close4
Deoxyribozyme-loaded nano-graphene oxide for simultaneous sensing and silencing of the hepatitis C virus gene in liver cells
No full textThe multifunctional DNAzyme (Dz) delivery system is developed based on nano-sized graphene oxide (nGO) for simultaneous detection and knockdown of the target gene. The Dz/nGO
complex system allowed convenient monitoring of HCV mRNA in living cells and silencing of the HCV gene expression by Dz-mediated catalytic cleavage concurrently.134331sciescopu
생기능성 나노물질에 의한 올리고핵산 약물전달, 세포 반응, RNA 감지에 관한 연구
No full text학위논문(박사) - 한국과학기술원 : 화학과, 2012.8,[xi, 122 p. :]Gene therapy may be therapeutically useful in relieving symptoms and treating any kind of diseases which hybridize with their complementary target site in mRNA, blocking translation to protein expression of patho-physiologic genes. These strategies include DNAzymes, siRNA, antisense oligonucleotides (ASO), ribozymes, and aptamers. Among these molecules, deoxyribozymes (DNAzyme, Dz) have been paid attention as therapeutics both in cell-based assays and in preclinical models of diseases including cancer and viral infectious diseases. The “10-23” RNA cleaving DNAzyme has been shown to cleave any purine-pyrimidine junction under simulated physiological conditions, therefore efficiently inhibiting expression of target proteins in vitro and in vivo studies. These molecules ideally combine the catalytic activity of ribozymes with the stability of oligodeoxynucleotides, are easy to synthesize and less sensitive to chemical and enzymatic degradation than RNA-based reagents. Factors to influence the eventual therapeutic use of DNAzymes include its efficient cellular uptake, subcellular localization, and stability. A particularly important challenge to achieve the successful down-regulation of gene expression is to deliver DNAzymes efficiently to its intended site of action.
Since various nanomaterials have unique, useful chemical, physical, and mechanical properties, they can be used for a wide variety of applications including nano-based biosensors, drug delivery devices, diagnostic tools, and means for tissue engineering and fundamental cell biology studies, etc.
In chapter 2, we describe synthesis and characterization of a multifunctional magnetic nanoparticle (MION) for both noninvasive in vivo imaging and delivery of DNAzyme to target organ for hepatitis C treatment. Hepatitis C is one of the infectious diseases in the liver caused by the hepatitis C virus (HCV), a small-sized, enveloped, positive sense single strand RNA virus. The multifunctional nanoparticles consist of magnetic nanoparticles labeled with near-infrared fluorescent dye and conjugated to a synthetic DNAzyme targeting a gene of interest. In addition, these nanoparticles are tailored with cell-penetrating peptides (CPPs) helping membrane translocation process. We demonstrated the silencing effect of a gene of interest by Dz-loaded multifunctional nanoparticles in cultured human liver cells (Huh-7). For in vivo study in mice, we performed the alkaline phosphatase activity assay using sera to measure the efficiency of DNA transfection, and found that the hydrodynamic delivery of the reporter plasmid elicited and was maintained over-expression in mice for some periods. The delivery of the nanoparticles would be monitored in dual fashions in vitro and in vivo. We believe that our Dz-conjugated nanoparticles will be one of the widely applicable therapeutic options for the efficient HCV treatment in near future.
Carbon based nanomaterials have shown much interest due to their unique structural and electrical properties such as mechanical strength, flexibility, electrical transport capability, young’s modulus, lightness and chemical inertness. Especially, graphene has the infinite possibilities to serve as novel nanoscale building blocks to create distinctive macroscopic materials. Due to their outstanding thermal and mechanical properties and high electrical conductivity, graphene sheets have been considered as a promising candidate for nanoelectronic devices, quantum computer, transparent electrode, and nanocomposite materials.
Conductive substrate show great potential in biological applications such as tissue engineering, implants, drug delivery carriers, biochips for diagnostics and nano-devices for biological study. Substrates for immobilizing cells and tissues are valuable in use of biological and medical field study. The adhesion and spreading of mammalian cells is mediated by the binding of cell-surface integrin receptors to peptide ligands from the extracellular matrix (ECM) and the clustering of these receptors into focal adhesion complexes. Integrins play a critical role in the formation of focal adhesions, which attach cells to the extracellular matrix. It has been reported that the interaction between cells and ECM depends on the multiple substrate characters such as chemical composition, geometry, and topological aspects, ligand organization, and substrate stiffness. In addition, these factors of engineered substrates based on nanomaterials can affect and even lead to various cellular responses and cell physiology. Little is to investigate their properties that make the influence of carbon based nanomaterials including graphene sheet on living system. While the advancements in technology may be considerable, there is also concern about unintended effects of exposure to nanomaterials.
In chapter 3, the chemically modified graphene oxides were immobilized on the glass substrates and used as a substrate for mammalian cells as a model of biological system to examine their influence on cell adhesion, spreading pattern and proliferation by various assays. We believe our result could serve as a fundamental standard for biological investigation of chemically prepared graphene-based nanomaterials.
As biomolecules inside cells including proteins, nucleic acids, and small molecules show a variety of expression level and pattern, localization or distribution, they are considered as the critical parameters that reflect the state of organism including cellular behaviors, function, proliferation, development, physiological and pathological states. In that point of view, the build-up of the biomolecule detection method is one of the important issues in the biomedical field for the treatment process of all sorts of diseases.
MicroRNAs (miRNAs) are a class of small-sizes (10~25nt) and non-coding RNA molecules that play an important regulatory role in the expression of diverse genes. Interestingly, miRNAs as the attractive biomolecule have been paid great attentions in a wide range of biological processes like development and metabolism and pathological progresses of disease/ disorders. Here, we fabricated the microRNA analytical platform for rapid, simple, and sensitive detection using nano-sized graphene oxide and detection probe PNA (peptide nucleic acid) for this study.
In chater 4, we evaluated that 1) the probe-nanographene complex can work as microRNA sensing platform with efficient fluorescence quenching and recovery ability, 2) nanographene oxide sheets can serve as a delivery carrier of detection probe into live cells for real-time monitoring and quantitative analysis of microRNA and 3) the nanogrpahene oxide sheets provide the stable loading platform in the complex biological solutions and samples.한국과학기술원 :화학과
Design of bimetallic nanoparticles
No full textThis work was supported by Korean Research Foundation Grant(KRF-2003-003-D00087). The author(S.J.Cho) acknowledged the generous permission to use the synchortron radiation at the Pohang Accelerator Laboratory
Syntheses of high quality KIT-6 and SBA-15 mesoporous silicas using low-cost water glass, through rapid quenching of silicate structure in acidic solution
No full textKIT-6 and SBA-15 ordered mesoporous silicas were obtained under various synthesis conditions using water glass as a low-cost silica source. The products were characterized with X-ray powder diffraction, N(2) adsorption, transmission electron microscopy, and scanning electron microscopy. The result showed that the initial mixing condition was a decisive factor for the structural order and mesoporosity. High-quality KIT-6 and SBA-15, even better than products from tetraethoxysilane, were obtained when the reactants were mixed very rapidly to cause instant quenching of silicate structures in acidic solution containing non-ionic surfactants. This procedure was highly reproducible and suitable for a large-scale synthesis. (C) 2009 Elsevier Inc. All rights reserved.This work was supported by the National Honor Scientist Program
of the Korean Ministry of Science and Technology. 29Si
NMR measurement was performed by a support from Korea Basic
Science Institute
A Synthetic Route to Ordered Mesoporous Carbon Materials with Graphitic Pore Walls
No full textThis work was supported in part by the Creative Research Initiative Program of the Korean Ministry of Science and Technology, and by the School of Molecular Science through the Brain Korea 21 project. The authors also thank Iljin Nanotech for the donation of multiwalled carbon nanotube samples, and LG Chem Research Park for Raman spectroscopy measurements
sj-docx-1-tam-10.1177_17588359221097190 – Supplemental material for Real-world outcomes of adjuvant gemcitabine versus gemcitabine plus capecitabine for resected pancreatic ductal adenocarcinoma
No full textSupplemental material, sj-docx-1-tam-10.1177_17588359221097190 for Real-world outcomes of adjuvant gemcitabine versus gemcitabine plus capecitabine for resected pancreatic ductal adenocarcinoma by Sora Kang, Changhoon Yoo, So Heun Lee, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Jae Ho Jeong, Do Hyun Park, Dong Wan Seo, Jin-hong Park, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Bong Jun Kwak, Sarang Hong, Heung-Moon Chang, Baek-Yeol Ryoo, Kyu-pyo Kim and Song Cheol Kim in Therapeutic Advances in Medical Oncology</p
Facile Synthesis of Monodispersed Mesoporous Silica Nanoparticles with Ultralarge Pores and Their Application in Gene Delivery
No full textAmong various nanoparticles, the silica nanoparticle (SiNP) is an attractive candidate as a gene delivery carrier due to advantages such as availability in porous forms for encapsulation of drugs and genes, large surface area to load biomacromolecules, biocompatibility, storage stability, and easy preparation in large quantity with low cost. Here, we report on a facile synthesis of monodispersed mesoporous silica nanoparticles (MMSN) possessing very large pores (> 15 nm) and application of the nanoparticles to plasmid DNA delivery to human cells. The aminated MMSN with large pores provided a higher loading capacity for plasmids than those with small pores (similar to 2 nm), and the complex of MMSN with plasmid DNA readily entered Into cells without supplementary polymers such as cationic dendrimers. Furthermore, MMSN with large pores could efficiently protect plasmids from nuclease-mediated degradation and showed much higher transfection efficiency of the plasmids encoding luciferase and green fluorescent protein. (pLuc, pGFP) compared to MMSN with small pores (similar to 2 nm).This work was supported by Basic
Science Research Program through the National Research
Foundation of Korea (NRF) funded by the Korean government
(MEST) (Grant Nos. 313-2008-2-C00538, 2008-0062074), by the
Nano R&D program of NRF funded by MEST (2008-2004457),
and by the National Honor Scientist Program (20100029665)
and World Class University Program (R31-2010-000-10071-0) of
NRF funded by MEST. H. Jeon was partially supported by a GRL
“Theragnosis” grant from the Korean Government (MEST) and
thanks the Advanced Analysis Center in KIST (Korea Institute of
Science & Technology) for use of the TEM
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