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Browsing by Author "Sung, Hsing-Wen"

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    Bioinspired Engineering of a Bacterium-Like Metal-Organic Framework for Cancer Immunotherapy
    (1970-01-01)
    Chen, Po-Ming
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    Pan, Wen-Yu
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    Miao, Yang-Bao
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    Liu, Yu-Miao
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    Luo, Po-Kai
    Bacteria-mediated tumor therapy (BMTT) has been known for decades; however, its clinical use is inhibited by its association with infections. To address this issue, a spiky, bacterium-like metal-organic framework (MOF), which can replicate the functional responses of BMTT without its adverse side-effects, is proposed. MOFs are synthesized in a solvothermal reaction of aluminum sulfate, ruthenium chloride hydrate, and 2-aminoterephthalic acid; they have a spherical morphology or many nanospikes on their surfaces, depending on the reaction temperature. Both spherical and spiky MOFs can function as photothermal agents, converting absorbed optical energy into local heat. Owing to their higher surface area of interaction, spiky MOFs are more easily phagocytosed by macrophages than are spherical MOFs, strengthening their immune responses. Moreover, when injected intratumorally, spiky MOFs reside significantly longer than spherical ones, enabling their use in repeated photothermal treatments. The combination of in situ vaccination with intratumorally injected bacterium-like MOFs under exposure to an near-infrared laser and the immune checkpoint blockade of systemically administered alpha PD-1 is evaluated in tumor-bearing mice. The results indicate that the checkpoint blockade acts synergistically with in situ vaccination to provide diverse antitumor functions of BMTT, destroying a primary tumor and suppressing tumor recurrence and metastasis.
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    Development of NS3/4A Protease-Based Reporter Assay Suitable for Efficiently Assessing Hepatitis C Virus Infection
    (2009-11-01)
    Pan, Kao-Lu
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    Lee, Jin-Ching
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    Sung, Hsing-Wen
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    Chang, Teng-Yuang
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    Hsu, John T. -A.
    A cell culture system for the production of hepatitis C virus (HCV) whole virions has greatly accelerated studies of the virus life cycle and the discovery of anti-HCV agents. However, the quantification of the HCV titers in a whole-virus infection/replication system currently relies mostly on reverse transcription-PCR or immunofluorescence assay, which would be cumbersome for high-throughput drug screening. To overcome this problem, this study has generated a novel cell line, Huh7.5-EG(Delta 4B5A) SEAP, that carries a dual reporter, EG(Delta 4B5A) SEAP. The EG(Delta 4B5A) SEAP reporter is a viral protease-cleavable fusion protein in which the enhanced green fluorescence protein is linked to secreted alkaline phosphatase (SEAP) in frame via Delta 4B5A, a short peptide cleavage substrate for NS3/4A viral protease. This study demonstrates that virus replication/infection in the Huh7.5-EG(Delta 4B5A) SEAP cells can be quantitatively indicated by measuring the SEAP activity in cell culture medium. The levels of SEAP released from HCV-infected Huh7.5-EG(Delta 4B5A) SEAP cells correlated closely with the amounts of HCV in the inocula. The Huh7.5-EG(Delta 4B5A) SEAP cells were also shown to be a suitable host for the discovery of anti-HCV inhibitors by using known compounds that target multiple stages of the HCV life cycle. The Z'-factorof this assay ranged from 0.64 to 0.74 in 96-well plates, indicating that this reporter system is suitable for high-throughput screening of prospective anti-HCV agents.
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    Pulsatile Drug Release from PLGA Hollow Microspheres by Controlling the Permeability of Their Walls with a Magnetic Field
    (2012-12-07)
    Chiang, Wei-Lun
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    Ke, Cherng-Jyh
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    Liao, Zi-Xian
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    Chen, San-Yuan
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    Chen, Fu-Rong