Browsing by Author "Cheng, Kai-Wen"

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460-nm InGaN-Based LEDs Grown on Fully Inclined Hemisphere-Shape-Patterned Sapphire Substrate With Submicrometer Spacing
(2009-10-01)
Chang, Chia-Ta
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Hsiao, Shih-Kuang
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Chang, Edward Yi
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Hsiao, Yu-Lin
;
Huang, Jui-Chien
This letter investigates 460-nm InGaN-based light-emitting diodes (LEDs) grown on a hemisphere-shape-patterned sapphire substrate (HPSS) with submicrometer spacing. The full-width at half-maximum of the (102) plane rocking curves for GaN layer grown on a conventional sapphire substrate (CSS) and HPSS are 480 and 262 arcsec, respectively. Such improvement is due to the reduction of the pure edge threading dislocations. At the forward current of 20 mA, the light output power of the LEDs grown on CSS and HPSS were 4.05 and 5.86 mW, respectively. This improvement of 44% light-output power can be attributed to the improved quality of the material and the increase of the light extraction by the fully inclined facets of the HPSS.
Bispecific antibody (HER2 x mPEG) enhances anti-cancer effects by precise targeting and accumulation of mPEGylated liposomes
(2020-07-15)
Chen, I-Ju
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Cheng, Yi-An
;
Ho, Kai-Wen
;
Lin, Wen-Wei
;
Cheng, Kai-Wen
Targeted antibodies and methoxy-PEGylated nanocarriers have gradually become a mainstream of cancer therapy. To increase the anti-cancer effects of targeted antibodies combined with mPEGylated liposomes (mPEG-liposomes), we describe a bispecific antibody in which an anti-methoxy-polyethylene glycol scFv (alpha mPEG scFv) was fused to the C-terminus of an anti-HER2 (alpha HER2) antibody to generate a HER2 x mPEG BsAb that retained the original efficacy of a targeted antibody while actively attracting mPEG-liposomes to accumulate at tumor sites. HER2 xmPEG BsAb can simultaneously bind to HER2high expressing MCF7/HER2 tumor cells and mPEG molecules on mPEG-liposomal doxorubicin (Lipo-Dox). Pre-incubation of HER2 x mPEG BsAb with cells increased the endocytosis of Lipo-DiD and enhanced the cytotoxicity of Lipo-Dox to MCF7/HER2 tumor cells. Furthermore, pre-treatment of HER2 x mPEG BsAb enhanced the tumor accumulation and retention of Lipo-DiR 2.2-fold in HER2-high expressing MCF7/HER2 tumors as compared to HER2-low expressing MCF7/neol tumors. Importantly, HER2 x mPEG BsAb plus Lipo-Dox significantly suppressed tumor growth as compared to control BsAb plus Lipo-Dox in MCF7/HER2 tumor-bearing mice. These results indicate that HER2 x mPEG BsAb can enhance tumor accumulation of mPEG-liposomes to improve the therapeutic efficacy of combination treatment. Anti-mPEG scFv can be fused to any kind of targeted antibody to generate BsAbs to actively attract mPEG-drugs and improve anti-cancer efficacy. Statement of Significance Antibody targeted therapy and PEGylated drugs have gradually become the mainstream of cancer therapy. To enhance the anti-cancer effects of targeted antibodies combined with PEGylated drugs is very important. To this aim, we fused an anti-PEG scFv to the C-terminal of HER2 targeted antibodies to generate a HER2xmPEG bispecific antibody (BsAb) to retain the original efficacy of targeted antibody whilst actively attract mPEG-liposomal drugs to accumulate at tumor sites. The present study demonstrates pretreatment of HER2xmPEG BsAb can enhance tumor accumulation of mPEG-liposomal drugs to improve the therapeutic efficacy of combination treatment. Anti-mPEG scFv can be fused to any kind of targeted antibody to generate BsAbs to actively attract mPEG-drugs and improve anti-cancer efficacy. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Enhanced drug internalization and therapeutic efficacy of PEGylated nanoparticles by one-step formulation with anti-mPEG bispecific antibody in intrinsic drug-resistant breast cancer
(2019-08-01)
Cheng, Yi-An
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Chen, I-Ju
;
Su, Yu-Cheng
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Cheng, Kai-Wen
;
Lu, Yun-Chi
For those patients with HER2-overexpressing breast cancer, treatment with PEGylated liposomal doxorubicin (PLD) is inefficacious due to the intrinsic low sensitivity to doxorubicin. A very large increase in drug accumulation by active targeting may enhance the therapeutic efficacy of PLD. We established a humanized bispecific antibody (BsAb; mPEG x HER2) which has dual specificity for methoxy-polyethylene glycol (mPEG) and human epidermal growth factor receptor 2 (HER2) to enhance the specificity, internalization and anticancer activity of PLD for cancer cells that overexpress HER2. One-step formulation of PLD with mPEG x HER2 converted the PLD into HER2 targeted liposomes that were stable at 4 degrees C in PBS as well as at 37 degrees C in the presence of serum. alpha HER2/PLD induced receptor-mediated endocytosis and enhanced doxorubicin accumulation in MCF7/HER2 (HER2-amplified) breast cancer cells. alpha HER2/PLD also displayed more than 200-fold increased cytotoxicity to MCF7/HER2 cells and 28-fold increased cytotoxicity to drug-resistant MDA-MB-361 cells with a physical deletion of the TOP2A gene. alpha HER2/PLD specifically accumulated doxorubicin in the nucleus of cancer cells in tumor-bearing mice and produced significantly greater antitumor activity against MCF7/HER2 (P < 0.0001) and MDA-MB-361 (P < 0.05) tumors as compared to untargeted PLD. Furthermore, the cardiotoxicity of alpha HER2/PLD was similar to that of PLD in human cardiomyocytes and in mice. Our results indicate that the one-step formulation of PLD by mPEG x HER2 is a simple method to confer tumor specificity, increase drug internalization and enhance the anticancer activity of PLD against HER2-overexpressing and doxorubicin-resistant breast cancer.
Fluid Modeling of a Nitrogen Atmospheric-Pressure Planar Dielectric Barrier Discharge Driven by a Realistic Distorted Sinusoidal Alternating Current Power Source
(2012-11-01)
Cheng, Kai-Wen
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Hung, Chieh-Tsan
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Lin, Kun-Mo
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Chiu, Yuan-Ming
;
Wu, Jong-Shinn
One-dimensional self-consistent simulations of a parallel-plate atmospheric-pressure nitrogen dielectric barrier discharge (DBD) are presented. The DBD was driven by a realistic distorted-sinusoidal voltage power source with a frequency of 60 kHz. The simulated discharge currents are in quantitative agreement with experimental measurements. N-4(+) ions gain more of the input electric power than electrons, which is unlike most glow discharges. The densities of all charged and neutral species increase exponentially with increasing applied peak voltage in the range of 6.2-8.6 kV. The higher the permittivity of the dielectric material, the larger the discharge current and the longer the period of gas breakdown. In addition, the quantity of accumulated charges at each electrode increases with increasing permittivity of the dielectric material. Finally, the increase in dielectric thickness from 1.0 to 2.0mm greatly reduces the densities of all species and also the plasma absorbed by the power. (C) 2012 The Japan Society of Applied Physics
Relation between the plasma characteristics and physical properties of functional zinc oxide thin film prepared by radio frequency magnetron sputtering process
(2010-02-01)
Hsu, Che-Wei
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Cheng, Tsung-Chieh
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Huang, Wen-Hsien
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Wu, Jong-Shinn
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Cheng, Cheng-Chih
The ZnO thin film was deposited on a glass substrate by a RF reactive magnetron sputtering method. Results showed that plasma density, electron temperature, deposition rate and estimated ion bombardment energy increase with increasing applied RF power. Three distinct power regimes were observed, which are strongly cot-related with plasma properties. In the low-power regime, the largest grain size was observed due to slow deposition rate. In the medium-power regime, the smallest grain size was found, which is attributed to insufficient time for the adatoms to migrate on substrate surface. In the high-power regime, relatively larger grain size was found due to very large ion bombardment energy which enhances the thermal migration of adatoms. Regardless of pure ZnO thin film or ZnO on glass, high transmittance (>80%) in the visible region can be generally observed. However, the film thickness plays a more important role for controlling optical properties, especially in the UV region, than the applied RF power. In general, with properly coated ZnO thin film, we can obtain a glass substrate which is highly transparent in the visible region, is of good anti-UV characteristics, and is highly hydrophobic, which is highly suitable for applications in the glass industry. (C) 2009 Elsevier B.V. All rights reserved.
Selective antibody activation through protease-activated pro-antibodies that mask binding sites with inhibitory domains
(2017-09-14)
Chen, I-Ju
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Chuang, Chih-Hung
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Hsieh, Yuan-Chin
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Lu, Yun-Chi
;
Lin, Wen-Wei
Systemic injection of therapeutic antibodies may cause serious adverse effects due to on-target toxicity to the antigens expressed in normal tissues. To improve the targeting selectivity to the region of disease sites, we developed protease-activated pro-antibodies by masking the binding sites of antibodies with inhibitory domains that can be removed by proteases that are highly expressed at the disease sites. The latency-associated peptide (LAP), C2b or CBa of complement factor 2/B were linked, through a substrate peptide of matrix metalloproteinase-2 (MMP-2), to an anti-epidermal growth factor receptor (EGFR) antibody and an anti-tumor necrosis factor-alpha (TNF-alpha) antibody. Results showed that all the inhibitory domains could be removed by MMP-2 to restore the binding activities of the antibodies. LAP substantially reduced (53.8%) the binding activity of the anti-EGFR antibody on EGFR-expressing cells, whereas C2b and CBa were ineffective (21% and 9.3% reduction, respectively). Similarly, LAP also blocked 53.9% of the binding activity of the anti-TNF-alpha antibody. Finally, molecular dynamic simulation showed that the masking efficiency of LAP, C2b and CBa was 33.7%, 10.3% and -5.4%, respectively, over the binding sites of the antibodies. This strategy may aid in designing new protease-activated pro-antibodies that attain high therapeutic potency yet reduced systemic on-target toxicity.