Browsing by Author "Chao, Jui-I"

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A general strategy to achieve ultra-high gene transfection efficiency using lipid-nanoparticle composites
(2014-09-01)
Vankayala, Raviraj
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Chiang, Chi-Shiun
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Chao, Jui-I
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Yuan, Chiun-Jye
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Lin, Shyr-Yeu
Gene therapy provides a new hope for previously "incurable" diseases. Low gene transfection efficiency, however, is the bottle-neck to the success of gene therapy. It is very challenging to develop non-viral nanocarriers to achieve ultra-high gene transfection efficiencies. Herein, we report a novel design of "tight binding-but-detachable" lipid-nanoparticle composite to achieve ultrahigh gene transfection efficiencies of 60 similar to 82%, approaching the best value (similar to 90%) obtained using viral vectors. We show that Fe@CNPs nanoparticles coated with LP-2000 lipid molecules can be used as gene carriers to achieve ultra-high (60-80%) gene transfection efficiencies in HeLa, U-87MG, and TRAMP-C1 cells. In contrast, Fe@CNPs having surface-covalently bound N,N,N-trimethyl-N-2-methacryloxyethyl ammonium chloride (TMAEA) oligomers can only achieve low (23-28%) gene transfection efficiencies. Similarly ultrahigh gene transfection/expression was also observed in zebrafish model using lipid-coated Fe@CNPs as gene carriers. Evidences for tight binding and detachability of DNA from lipid-nanoparticle nanocarriers will be presented. (C) 2014 Elsevier Ltd. All rights reserved.
A novel compound PT-262 inhibits Oct4 and Nanog on the survivin blockage and apoptosis induction in human lung cancer
(2016-04-01)
Chen, Yan-Ting
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Li, Jing-Yi
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Pan, Pei-Ying
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Chen, Chin-Piao
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Chao, Jui-I
A novel compound PT-262 inhibits Oct4 and Nanog on the survivin blockage and apoptosis induction in human lung cancer
(2016-04-01)
Chen, Yan-Ting
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Li, Jing-Yi
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Pan, Pei-Ying
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Chen, Chin-Piao
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Chao, Jui-I
A novel EGFR inhibitor SP101 blocks survivin and tumor growth in the human non-small cell lung carcinoma
(2015-04-01)
Chao, Jui-I
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Wang, Su-Pei
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Wu, Ya-Hui
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Yang, Jinn-Moon
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Chen, Chinpiao
A novel synthetic compound overcomes drug resistance on EGFR (T790M) and cancer stemness in human non-small cell lung cancer
(2017-04-01)
Pan, Pei Ying
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Chang, Chien-Jen
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Liu, Kuang-Kai
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Chan, Yu-Chi
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Chen, Yan-Ting
Activation of p38 mitogen-activated protein kinase by celecoxib oppositely regulates survivin and gamma-H2AX in human colorectal cancer cells
(2007-07-01)
Hslao, Po-Wen
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Chang, Chia-Ching
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Liu, Huel-Fang
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Tsai, Chuan-Mei
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Chiu, Ted H.
Cancer cells express survivin that facilitates tumorigenesis. Celecoxib has been shown to reduce human colorectal cancers. However, the role and regulation of survivin by celecoxib in colorectal carcinoma cells remain unclear. Treatment with 40-80 mu M celecoxib for 24 h induced cytotoxicity and proliferation inhibition via a concentration-dependent manner in RKO colorectal carcinoma cells. Celecoxib blocked the survivin protein expression and increased the phosphorylation of H2AX at serine- 193 (gamma-H2AX). The survivin gene knockdown by transfection with a survivin siRNA revealed that the loss of survivin correlated with the expression of gamma-H2AX. Meanwhile, celecoxib increased caspase-3 activation and apoptosis. Celecoxib activated the phosphorylation of p38 mitogen-activated protein (MAP) kinase. The phosphorylated proteins of p38 MAP kinase and gamma-H2AX were observed in the apoptotic cells. SB203580, a specific p38 MAP kinase inhibitor, protected the survivin protein expression and decreased the levels of gamma-H2AX and apoptosis in the celecoxib-exposed cells. The blockade of survivin expression increased the celecoxib-induced cytotoxicity; conversely, overexpression of survivin by transfection with a survivin -expressing vector raised the cancer cell proliferation and resisted the celecoxib-induced cell death. Our results provide for the first time that p38 MAP kinase participates in the down-regulation of survivin and subsequently induces the activation of gamma-H2AX for mediating apoptosis following treatment with celecoxib in human colorectal cancer cells. (c) 2007 Elsevier Inc. All rights reserved.
Alpha-bungarotoxin binding to target cell in a developing visual system by carboxylated nanodiamond
(2008-05-21)
Liu, Kuang-Kai
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Mei-Fang Chen
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Chen, Po-Yi
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Lee, Tony J. F.
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Cheng, Chia-Liang
Biological molecules conjugating with nanoparticles are valuable for applications including bio-imaging, bio-detection, and bio-sensing. Nanometer-sized diamond particles have excellent electronic and chemical properties for bio-conjugation. In this study, we manipulated the carboxyl group produced on the surface of nanodiamond (carboxylated nanodiamond, cND) for conjugating with alpha-bungarotoxin (alpha-BTX), a neurotoxin derived from Bungarus multicinctus with specific blockade of alpha7-nicotinic acetylcholine receptor (alpha 7-nAChR). The electrostatic binding of cND-alpha-BTX was mediated by the negative charge of the cND and the positive charge of the alpha-BTX in physiological pH conditions. Sodium dodecyl sulfate-polyacrylamide gel analysis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF-MS) spectra displayed that alpha-BTX proteins were conjugated with cND particles via non-covalent bindings. The green fluorescence of the cND particles combining with the red fluorescence of tetramethylrhodamine-labeled a-BTX presented a yellow color at the same location, which indicated that alpha-BTX proteins were conjugated with cND particles. Xenopus laevis's oocytes expressed the human alpha 7-nAChR proteins by microinjection with alpha 7-nAChR mRNA. The cND-alpha-BTX complexes were bound to alpha 7-nAChR locating on the cell membrane of oocytes and human lung A549 cancer cells analyzed by laser scanning confocal microscopy. The choline-evoked alpha 7-nAChR-mediated inward currents of the oocytes were blocked by cND-alpha-BTX complexes in a concentration-dependent manner using two-electrode voltage-clamp recording. Furthermore, the fluorescence intensity of cND-alpha-BTX binding on A549 cells could be quantified by flow cytometry. These results indicate that cND-conjugated alpha-BTX still preserves its biological activity in blocking the function of alpha 7-nAChR, and provide a visual system showing the binding of alpha-BTX to alpha 7-nAChR.
Bio-imaging of alpha-bungarotoxin binding to target cell by carboxylated nanodiamond
(2008-04-01)
Chao, Jui-I
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Liu, Kuang-Kai
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Chen, Mei-Fang
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Chen, Po-Yi
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Lee, Tony J. F.
Biocompatible and detectable carboxylated nanodiamond on human cell
(2007-08-15)
Liu, Kuang-Kai
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Cheng, Chia-Liang
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Chang, Chia-Ching
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Chao, Jui-I
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生物科技學系
Surface-modified carboxylated nanometre-sized diamond (cND) has been applied for the conjugation of biological molecules such as DNA and protein. In this study, we evaluated the biocompatibility and detection of cNDs and carbon nanotubes on human lung A549 epithelial cells and HFL-1 normal fibroblasts. Treatment with 5 or 100 nm cND particles, 0.1 - 100 mu g ml(-1), did not reduce the cell viability and alter the protein expression profile in lung cells; however, carbon nanotubes induced cytotoxicity in these cells. The cNDs particles were accumulated in A549 cells, which were observed by atomic force microscopy and laser scanning confocal microscopy. Both 5 and 100 nm cNDs particles exhibited the green fluorescence and were ingested into cells. Moreover, the fluorescence intensities were increased in cells via a concentration-dependent manner after treatment with 5 and 100 nm cNDs, which can be detected by flow cytometer analysis. The fluorescence intensities of 5 nm cNDs were relative higher than 100 nm cNDs in cells at equal concentration treatment. The observation demonstrated that cND-interacting with cell is detectable by a confocal microscope, flow cytometer and atomic force microscope. These nanoparticles may be useful for further biomedical applications based on the properties of uptake ability, detectability and little cytotoxicity in human cells.
Biocompatible evaluation of fluorescent nanodiamonds in neurons in vitro
(2014-04-01)
Kao, Jun-Wei
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Huang, Yung-An
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Chiang, Ming-Han
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Huang, Hou-Syun
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Liu, Kuang-Kai
CARRIER COMPRISING NANODIAMOND
(2011-01-13)
Chao, Jui-I
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Chen, Chin-Piao
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Cheng, Chia-Liang
The present invention provides a carrier including a nanodiamond (ND) particle and a linker covalently bound to the ND particle, in which the linker is presented by the formula: —R1—O(R2)m-Q-. In addition, the present invention further provides a carrier having an active unit covalently bound to the linker, in which the active unit is a drug, a vitamin or a biological molecule.
Celecoxib induces p53-PUMA pathway for apoptosis in human colorectal cancer cells
(2008-10-22)
Liu, Huei-Fang
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Hsiao, Po-Wen
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Chao, Jui-I
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生物科技學系
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Department of Biological Science and Technology
Celecoxib, a clinical non-steroidal anti-inflammatory drug, displays anticarcinogenic and chemopreventive activities in human colorectal cancers, although the mechanisms of apoptosis by celecoxib are poorly understood. The existence of functional p53 but not securin in colorectal cancer cells was higher on the induction of cytotoxicity than the p53-mutational colorectal cancer cells following celecoxib treatment. The p53-wild type HCT116 cells were more susceptible to increase similar to 25% cell death than the p53-null HCT116 cells after treatment with 100 mu M celecoxib for 24 h.Transfection with a small interfering RNA of p53 reduced the celecoxib-induced cytotoxicity in the RKO (p53-wild type) colorectal cancer cells. Celecoxib (80-100 mu M for 24 h) significantly increased total p53 proteins and the phosphorylated p53 proteins at serine-15,-20,-46, and -392 in RKO cells. However, the phospho-p53 (serine-15, 20, and -392) proteins were presented on the nuclei of cells but the phospho-p53 (serine-46) protein was located on the cytoplasma of apoptotic cells following treatment with celecoxib. Interestingly, the p53 up-regulated modulator of apoptosis (PUMA) protein, which located on the mitochondria, was induced by celecoxib in the p53-functional colorectal cancer cells but not in the p53-mutational cells. Together, this study provides the first time that celecoxib induces the various phosphorylated sites of p53 and activates p53-PUMA pathway, which potentiates the apoptosis induction in human colorectal cancer cells. Crown Copyright (c) 2008 Published by Elsevier Ireland Ltd. All rights reserved.
Chasing nanodiamond in cell cycle progression
(2009-04-01)
Chao, Jui-I
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Liu, Kuang-Kai
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生物科技學系
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Department of Biological Science and Technology
Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition
(2017-08-29)
Lin, Yu-Wei
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Raj, Emmanuel Naveen
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Liao, Wei-Siang
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Lin, Johnson
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Liu, Kuang-Kai
The poor intracellular uptake and non-specific binding of anticancer drugs into cancer cells are the bottlenecks in cancer therapy. Nanocarrier platforms provide the opportunities to improve the drug efficacy. Here we show a carbon-based nanomaterial nanodiamond (ND) that carried paclitaxel (PTX), a microtubule inhibitor, and cetuximab (Cet), a specific monoclonal antibody against epidermal growth factor receptor (EGFR), inducing mitotic catastrophe and tumor inhibition in human colorectal cancer (CRC). ND-PTX blocked the mitotic progression, chromosomal separation, and induced apoptosis in the CRC cells; however, NDs did not induce these effects. Conjugation of ND-PTX with Cet (ND-PTX-Cet) was specifically binding to the EGFR-positive CRC cells and enhanced the mitotic catastrophe and apoptosis induction. Besides, ND-PTX-Cet markedly decreased tumor size in the xenograft EGFR-expressed human CRC tumors of nude mice. Moreover, ND-PTX-Cet induced the mitotic marker protein phospho-histone 3 (Ser10) and apoptotic protein active-caspase 3 for mitotic catastrophe and apoptosis. Taken together, this study demonstrated that the co-delivery of PTX and Cet by ND enhanced the effects of mitotic catastrophe and apoptosis in vitro and in vivo, which may be applied in the human CRC therapy.
Combination of Aurora A and Haspin inhibitors enhances p53 expression and tumor growth inhibition in human colorectal cancer
(2016-04-01)
Chang, Yun-Hsuan
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Lin, Chien-I
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Chen, Zan-Chu
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Liu, Kuang-Kai
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Chao, Jui-I
Combination of Aurora A and Haspin inhibitors enhances p53 expression and tumor growth inhibition in human colorectal cancer
(2016-04-01)
Chang, Yun-Hsuan
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Lin, Chien-I
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Chen, Zan-Chu
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Liu, Kuang-Kai
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Chao, Jui-I
Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy
(2010-08-06)
Liu, Kuang-Kai
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Zheng, Wen-Wei
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Wang, Chi-Ching
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Chiu, Yu-Chung
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Cheng, Chia-Liang
A nanoparticle-conjugated cancer drug provides a novel strategy for cancer therapy. In this study, we manipulated nanodiamond (ND), a carbon nanomaterial, to covalently link paclitaxel for cancer drug delivery and therapy. Paclitaxel was bound to the surface of 3-5 nm sized ND through a succession of chemical modifications. The ND-paclitaxel conjugation was measured by atomic force microscope and nuclear magnetic resonance spectroscopy, and confirmed with infrared spectroscopy by the detection of deuterated paclitaxel. Treatment with 0.1-50 mu g ml(-1) ND-paclitaxel for 48 h significantly reduced the cell viability in the A549 human lung carcinoma cells. ND-paclitaxel induced both mitotic arrest and apoptosis in A549 cells. However, ND alone or denatured ND-paclitaxel (after treatment with strong alkaline solution, 1 M NaOH) did not induce the damage effects on A549 cells. ND-paclitaxel was taken into lung cancer cells in a concentration-dependent manner using flow cytometer analysis. The ND-paclitaxel particles were located in the microtubules and cytoplasm of A549 cells observed by confocal microscopy. Furthermore, ND-paclitaxel markedly blocked the tumor growth and formation of lung cancer cells in xenograft SCID mice. Together, we provide a functional covalent conjugation of ND-paclitaxel, which can be delivered into lung carcinoma cells and preserves the anticancer activities on the induction of mitotic blockage, apoptosis and anti-tumorigenesis.
CR108, a novel vitamin K3 derivative induces apoptosis and breast tumor inhibition by reactive oxygen species and mitochondrial dysfunction
(2013-12-15)
Yang, Chun-Ru
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Liao, Wei-Siang
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Wu, Ya-Hui
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Murugan, Kaliyappan
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Chen, Chinpiao
Vitamin K3 derivatives have been shown to exert anticancer activities. Here we show a novel vitamin K3 derivative (S)-2-(2-hydroxy-3-methylbutylthio)naphthalene-1,4-dione, which is named as CR108 that induces apoptosis and tumor inhibition through reactive oxygen species (ROS) and mitochondrial dysfunction in human breast cancer. CR108 is more effective on the breast cancer cell death than other vitamin K3 derivatives. Moreover, CR108 induced apoptosis in both the non-HER-2-overexpressed MCF-7 and HER-2-overexpressed BT-474 breast cancer cells. CR108 caused the loss of mitochondrial membrane potential, cytochrome c released from mitochondria to cytosol, and cleaved PARP proteins for apoptosis induction. CR108 markedly increased ROS levels in breast cancer cells. N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the CR108-induced ROS levels, mitochondrial dysfunction and apoptosis. Interestingly, CR108 increased the phosphorylation of p38 MAP kinase but conversely inhibited the survivin protein expression. NAC treatment prevented the activation of p38 MAP kinase and rescued the survivin protein levels. SB202190, a specific p38 MAP kinase inhibitor, recovered the survivin protein levels and attenuated the cytotoxicity of CR108-treated cells. Furthermore, CR108 inhibited the xenografted human breast tumor growth in nude mice. Together, we demonstrate that CR108 is a novel vitamin K3 derivative that induces apoptosis and tumor inhibition by ROS production and mitochondrial dysfunction and associates with the phosphorylation of p38 MAP kinase and the inhibition of survivin in the human breast cancer. (C) 2013 Elsevier Inc All rights reserved.
Delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition in colorectal cancer
(2016-04-01)
Lin, Yu-Wei
;
Liao, Wei-Siang
;
Lin, Johnson
;
Liu, Kuang-Kai
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Cheng, Hsiao-Chun
Delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition in colorectal cancer
(2016-04-01)
Lin, Yu-Wei
;
Liao, Wei-Siang
;
Lin, Johnson
;
Liu, Kuang-Kai
;
Cheng, Hsiao-Chun