Browsing by Author "Chen, Jen-Kun"

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Development of a Novel Shallow Liquid Interface Exposure System for MWCNT Toxicity Assessment
(2019-10-01)
Tien, Chi-Yu
;
Li, Jui-Ping
;
Han, Ding
;
Li, Ziyi
;
Fu, Pin-Kuei
Increasing applications of multiwalled carbon nanotubes (MWCNT) lead to significant occupational exposure and potential health concerns. Toxicity of MWCNT should be carefully elucidated since the conventional (CON) method with fully immersed condition fails to mimic the air-liquid interface (ALI) in airways. Additionally, quantification of MWCNT in cells was a real challenge. Currently available ALI exposure devices are costly, posing problems to conducting in vitro evaluations for emerging nanomaterials. A novel system, consisting of a shaker fluidized-bed atomizer (SFA) and electrostatic shallow liquid interface (ESLI) exposure chamber, has been developed for investigating nanotoxicity of well-dispersed pristine-MWCNT (pMWCNT) and carboxylized-MWCNT (cMWCNT). After 24-h exposure, LDH, MCP-1, IL-1 beta, IL-6, and TNF-alpha releases were determined, and cell uptakes were quantified according to the molybdenum content in cells. Biological responses triggered by SLI exposure are obviously more sensitive compared with those caused by CON exposure at equivalent doses. Exposure dose-dependent release of LDH and IL-6 was highlighted in A549 cells, indicating higher cytotoxicity and inflammatory responses of cMWCNT attributed to its shorter length, smaller size, and higher cell uptake. Cell-associated dose-dependent release of LDH and IL-6 was highlighted in RAW264.7 cells, revealing the higher adverse health risk of pMWCNT due to frustrated phagocytosis and its much higher molybdenum content. These results suggest that inherent characteristics of cells and distinct physicochemical properties of pMWCNT and cMWCNT lead to either exposure dose-dependent or cell-associated dose-dependent responses. Notably, the SLI is superior to the CON exposure method and well suited for nanotoxicity assessment of different MWCNTs.
Directly Thiolated Modification onto the Surface of Detonation Nanodiamonds
(2014-05-28)
Hsu, Ming-Hua
;
Chuang, Hong
;
Cheng, Fong-Yu
;
Huang, Ying-Pei
;
Han, Chien-Chung
An efficient method for modifying the surface of detonation nanodiamonds (5 and 100 nm) with thiol groups (-SH) by using an organic chemistry strategy is presented herein. Thiolated nanodiamonds were characterized by spectroscopic techniques, and the atomic percentage of sulfur was analyzed by elemental analysis and X-ray photoelectron spectroscopy. The conjugation between thiolated nanodiamonds and gold nanoparticles was elucidated by transmission electron microscopy and UV-vis spectrometry. Moreover, the material did not show significant cytotoxicity to the human lung carcinoma cell line and may prospectively be applied in bioconjugated technology. The new method that we elucidated may significantly improve the approach to surface modification of detonation nanodiamonds and build up a new platform for the application of nanodiamonds.
Exposure assessment of process by-product nanoparticles released during the preventive maintenance of semiconductor fabrication facilities
(2018-07-20)
Liao, Bo-Xi
;
Tseng, Neng-Chun
;
Li, Ziyi
;
Liu, Yingshu
;
Chen, Jen-Kun
This study characterized the process by product particles (mostly nanoparticles) released during the preventive maintenance of semiconductor fabrication facilities, such as chemical mechanical planarization (CMP), plasma-enhanced chemical vapor deposition (PECVD), and ion implantation. Manual sampling and real-time measurements with direct reading instruments were conducted to assess the exposure levels of nanoparticles and their physical and chemical properties. Significant amount of nanoparticles were observed in the breathing zone of the workers during the maintenance of the PECVD and ion implanters with the peak number concentrations as high as 6,470,000 and 65,444 #/cm(3), respectively, indicating that the deposited residual chemicals in the reaction chambers were released as airborne nanoparticles by the maintenance activities. In contrast, nanoparticles released during the maintenance of the local scrubber, CMP, and replacing CMP slurry drums were insignificant. Causes of the particle release were discussed and suggestions were made to mitigate the nanoparticle release and reduce the exposure levels.
In-situ Formation and Assembly of Gold Nanoparticles by Gum Arabic as Efficient Photothermal Agent for Killing Cancer Cells
(2013-10-01)
Liu, Ching-Ping
;
Lin, Fong-Sian
;
Chien, Chih-Te
;
Tseng, Sheng-Yang
;
Luo, Chih-Wei
Multifunctional silver nanocluster-hybrid oligonucleotide vehicle for cell imaging and microRNA-targeted gene silencing
(2017-04-01)
Chen, Hau-Yun
;
Albert, Karunya
;
Wen, Cheng-Che
;
Hsieh, Pei-Ying
;
Chen, Sih-Yu
Novel therapeutics is urgently needed to prevent cancer-related deaths. MicroRNAs that act as tumor suppressors have been recognized as a next-generation tumor therapy, and the restoration of tumor suppressive microRNAs using microRNA replacements or mimics may be a less toxic, more effective strategy due to fewer off-target effects. Here, we designed the novel multifunctional oligonucleotide nanocarrier complex composed of a tumor-targeting aptamer sequence specific to mucin 1. (MUC1), poly-cytosine region for fluorescent silver nanocluster (AgNC) synthesis, and complimentary sequence for microRNA miR-34a loading. MiR-34a was employed because of its therapeutic effect of inhibiting oncogene expression and inducing apoptosis in carcinomas. By monitoring the intrinsic fluorescence of AgNC, it was clearly shown that the constructed complex (MUC1-AgNCm-miR-34a) enters MCF-7 cells. To evaluate the efficacy of this nanocarrier for microRNA delivery, we investigated the gene and protein expression levels of downstream miR-34a targets (BCL-2, CDK6, and CCNDI) by quantitative PCR and western blotting, respectively, and the results indicated their effective inhibition by miR-34a. This novel multifunctional AgNC-based nanocarrier can aid in improving the efficacy of breast cancer theranostics. (C) 2017 Elsevier B.V. All rights reserved.
Prorenin receptor acts as a potential molecular target for pancreatic ductal adenocarcinoma diagnosis
(2016-08-23)
Arundhathi, Arivajiagane
;
Chuang, Wen-Han
;
Chen, Jen-Kun
;
Wang, Shin-E
;
Shyr, Yi-Ming
Recent studies have implicated the prorenin receptor (PRR) is associated with pancreatic tumorigenesis. We therefore investigated the role of PRR in pancreatic tumorigenesis and assessed whether PRR can serve as a target for imaging diagnosis at early stages of PDAC. Here we show that aberrant expression of PRR in premalignant PanIN lesions, and human PDAC samples, and PDAC cell lines, particularly in Panc-1 cells. Interestingly, PRR expression was positively associated with PDAC progression. Moreover, overexpression of human PRR resulted in increased cell proliferation and decreased apoptosis, while knockdown of human PRR caused decreased cell proliferation and enhanced apoptosis in pancreatic cancer cells. We also observed that overexpression of human PRR enhanced MAPK and PI3K/Akt signaling pathways in PDAC cells, while knockdown of human PRR suppressed both of pathways. The confocal imaging analysis showed that human PRR was highly expressed in Panc-1, ASPC, and Miapaca cells, whereas BXPC-3, and HPAC cells had a significantly lower fluorescent signals. Consistently, the single-photon emission computed tomography (SPET/CT) showed that the uptake of anti-PRR labelled with I-125 was higher in Panc-1 and ASPC tumors-bearing mice after 96 hours injection. Importantly, tumors in pancreas of Pdx1-cre; LSL-Kras(G12D) mice had a significant increased PRR expression and accumulation of radioactivity at 96 h after injection. These data suggest that I-125-anti-PRR can detect the orthotopic tumors in Pdx1-cre; LSL-Kras(G12D) mice. Therefore, anti-PRR labelled with I-125 is a promising radiotracer for imaging diagnosis at early stages of pancreatic cancer.
Synthesis and Evaluation of Aminothiazole-Paeonol Derivatives as Potential Anticancer Agents
(2016-02-01)
Tsai, Chia-Ying
;
Kapoor, Mohit
;
Huang, Ying-Pei
;
Lin, Hui-Hsien
;
Liang, Yu-Chuan
In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using H-1-NMR, C-13-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 mu M to AGS, 4.4 mu M to HT-29 cells and 5.8 mu M to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 mu M to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma.