Browsing by Author "Chen, Chia-Hung"

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7,7 ''-Dimethoxyagastisflavone-induced Apoptotic or Autophagic Cell Death in Different Cancer Cells
(2012-04-01)
Hwang, Chia-Hsiang
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Lin, Yu-Ling
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Liu, Yen-Ku
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Chen, Chia-Hung
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Wu, Hsin-Yi
7,7''-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus X media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells. Copyright (C) 2011 John Wiley & Sons, Ltd.
A fusion protein composed of receptor binding domain of vascular endothelial growth factor-A and constant region fragment of antibody: angiogenesis antagonistic activity
(2011-05-01)
Tseng, Feng-Jen
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Liu, Yen-Ku
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Chung, Yo-Shong
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Lin, Yu-Ling
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Chen, Chia-Hung
Vascular endothelial growth factor (VEGF) promotes the growth of solid tumor mainly via VEGF receptor-1 and receptor-2, which are expressed preferentially in proliferating endothelial cells. Therefore, a strategy for simultaneous blockage of both VEGF receptors may have a useful therapeutic effect in tumor growth. In this study, we utilized a fusion protein which is composed of receptor binding domain of VEGF-A (RBDV) and the constant region fragment (Fc) of a human immunoglobulin G1 (IgG1), to interfere with the growth of human umbilical vein endothelial cells (HUVECs) via VEGF receptors. The results showed that RBDV-IgG1 Fc was able to bind with both VEGF receptor-1 and receptor-2. In addition, RBDV-IgG1 Fc could decrease VEGF-induced proliferation and tube formation among HUVECs. Moreover, the cytotoxic test showed RBDV-IgG1 Fc could also enhance the cytotoxic activity of human natural killing cells. The data are suggesting that the fusion protein, RBDV-IgG1 Fc, may have potential as an angiogenesis antagonist for future tumor therapy.
A fusion protein with the receptor binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment
(2010-11-01)
Tseng, Feng-Jen
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Chen, Yu-Cheng
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Lin, Yu-Ling
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Tsai, Nu-Man
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Lee, Ru-Ping
Vascular endothelial growth factor (VEGF) is an angiogenic factor that signals through VEGFR-1 and VEGFR-2, which are expressed preferentially in proliferating endothelial cells. Thus, simultaneous blockage of both VEGF receptors may provide a more efficient therapeutic response in cancer treatment. We created a recombinant fusion protein (RBDV-IgG1 Fc), which is composed of the receptor binding domain of human VEGF-A (residues 8-109) and the Fc region of human IgG1 immunoglobulin. The recombinant protein can bind to both mouse VEGFR-1 and VEGFR-2 to decrease VEGF-induced proliferation and tube formation of endothelial cells in vitro. In this study, the RBDV-IgG1 Fc fusion protein reduced the effects of proliferation, migration and tube formation induced by VEGF in murine endothelial cells in vitro. In vivo tumor therapy with RBDV-IgG1 Fc resulted in tumor inhibition by reducing angiogenesis. Pathological evidence also shows that RBDV-IgG1 Fc can seriously damage vessels, causing the death of tumor cells. These findings suggest that this chimeric protein has potential as an angiogenesis antagonist in tumor therapy.
A Lipo-PEG-PEI complex for encapsulating curcumin that enhances its antitumor effects on curcumin-sensitive and curcumin-resistance cells
(2012-04-01)
Lin, Yu-Ling
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Liu, Yen-Ku
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Tsai, Nu-Man
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Hsieh, Jui-Hung
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Chen, Chia-Hung
A cationic liposome-PEG-PEI complex (LPPC) was used as a carrier for the encapsulation of hydrophobic curcumin to give curcumin/LPPC. Curcumin/LPPC had an average size less than 270 nm and a zeta potential of approximately 40 mV. The LPPC encapsulation efficiency for curcumin was about 45%. The authors found it surprising that the cytotoxic activity of the curcumin/LPPC was fivefold higher than curcumin when tested on curcumin-sensitive cells and 20-fold more active against curcumin-resistant cells. Curcumin/LPPC treatment caused a cell cycle arrest at G2/M phase, which rapidly resulted in apoptosis. The increased cytotoxic activity of curcumin/LPPC is likely attributable to its rapid accumulation in the cell. In vivo, administration of curcumin/LPPC inhibited about 60 - 90% of tumor growth in mice bearing CT-26 or B16F10 cells. These results demonstrate LPPC encapsulation technology is able to enhance the effects of antitumor drugs. Use of this technology may provide a new tool for cancer therapy, especially for drug-resistant cancer.
A panel of eight microRNAs is a good predictive parameter for triple-negative breast cancer relapse
(2020-01-01)
Hong, Hsiao-Chin
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Chuang, Cheng-Hsun
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Huang, Wei-Chih
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Weng, Shun-Long
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Chen, Chia-Hung
Rationale: Triple-negative breast cancer (TNBC), which has the highest recurrence rate and shortest survival time of all breast cancers, is in urgent need of a risk assessment method to determine an accurate treatment course. Recently, miRNA expression patterns have been identified as potential biomarkers for diagnosis, prognosis, and personalized therapy. Here, we investigate a combination of candidate miRNAs as a clinically applicable signature that can precisely predict relapse in TNBC patients after surgery. Methods: Four total cohorts of training (TCGA_TNBC and GEOD-40525) and validation (GSE40049 and GSE19783) datasets were analyzed with logistic regression and Gaussian mixture analyses. We established a miRNA signature risk model and identified an 8-miRNA signature for the prediction of TNBC relapse. Results: The miRNA signature risk model identified ten candidate miRNAs in the training set. By combining 8 of the 10 miRNAs (miR-139-5p, miR-10b-5p, miR-486-5p, miR-455-3p, miR-107, miR-146b-5p, miR-324-5p and miR-20a-5p), an accurate predictive model of relapse in TNBC patients was established and was highly correlated with prognosis (AUC of 0.80). Subsequently, this 8-miRNA signature prognosticated relapse in the two validation sets with AUCs of 0.89 and 0.90. Conclusion: The 8-miRNA signature predictive model may help clinicians provide a prognosis for TNBC patients with a high risk of recurrence after surgery and provide further personalized treatment to decrease the chance of relapse.
A RAPID AND CONVENIENT METHOD TO ENHANCE TRANSGENIC EXPRESSION IN TARGET CELLS
(2012)
Chen, Chia-Hung
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Liu, Yen-Ku
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Lin, Yu-Ling
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Chuang, Huai-Yao
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Hsu, Wei-Tung
Gene therapy provides a novel strategy and a new hope for patients with cancer. Unfortunately, the specifics of the delivery systems or the promoters have not achieved the specified efficacy so far, and the perfection of either system will be extremely difficult. In this study, we introduce a simple concept that a combination of a partially specific delivery system and a partially specific promoter activity may achieve a more specific effect on transgenic expression in target cells. The first section describes tumor-related transcription factors that were assayed in tumors or rapidly proliferating cells to determine their activities. The activities of nuclear factor (NF)-kappa B, CREB, and HIF-1 were higher, and three copies of each response element were used to construct a transcription factor-based synthetic promoter (TSP). The results showed that the expression of the TSP was active and partially specific to cell types. As described in the second section, the multifunctional peptide RGD-4-CHA was designed to absorb polyethyleneimine (PEI) molecules, and this complex was targeted to integrin alpha v beta 3 on B16F10 cells. The results indicated that RGD-4C-HA could associate with PEI to mediate specific targeting in vitro. Finally, the combination of the PEI-peptide complex and TSP could enhance the specifically transgenic expression in B16F10 cells. This strategy has been proven to work in vitro and might potentially be used for specific gene therapy in vivo.
A Soybean Oil-Based Liposome-Polymer Transfection Complex as a Codelivery Systemfor DNA and Subunit Vaccines
(2012)
Lin, Yu-Ling
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Chen, Li-Yi
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Chen, Chia-Hung
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Liu, Yen-Ku
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Hsu, Wei-Tung
Inexpensive liposome-polymer transfection complexes (LPTCs) were developed and used as for DNA or protein delivery. The particle sizes of the LPTCs were in the range of 212.2 to 312.1 nm, and the zetapotential was +38.7 mV. LPTCs condensed DNA and protected DNA from DNase I digestion and efficiently delivered LPTC/DNA complexes in Balb/3T3 cells. LPTCs also enhanced the cellular uptake of antigen in mouse macrophage cells and stimulated TNF-alpha release in naive mice splenocytes, both indicating the potential of LPTCs as adjuvants for vaccines. In vivo studies were performed using H. pylori relative heat shock protein 60 as an antigen model. The vaccination of BALB/c mice with LPTC-complexed DNA and protein enhanced the humoral immune response. Therefore, we developed a DNA and protein delivery system using LPTCs that is inexpensive, and we successfully applied it to the development of a DNA and subunit vaccine.
A Unique and Potent Protein Binding Nature of Liposome Containing Polyethylenimine and Polyethylene Glycol: A Nondisplaceable Property
(2011-06-01)
Liu, Yen-Ku
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Lin, Yu-Ling
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Chen, Chia-Hung
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Lin, Ching-Min
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Ma, Kuan-Lun
Most of the currently available targeting vectors are produced via the linkage of targeting molecules. However, the coupling process is complicated, and the covalent linkage may attenuate the activity of certain targeting molecules. In this study, we have developed a cationic liposome complexed with polyethylenimine and polyethylene glycol polymers (LPPC) that can capture various proteins without covalent conjugation. Characterizations of prepared LPPC revealed that the maximal-binding capacity was about 170 mu g of bovine serum albumin to 40 mu g of sphere-shaped LPPC (180 nm). The proteins were essentially located at or near the surface when analyzed by atomic force or transmission electron microscopy. We demonstrate that polyethylenimine was an essential component to bind the proteins. Upon the saturation of captured proteins, a given protein could not be displaced by other additional proteins and still retained its biological activity. Using a variety of functional proteins, we show some typical examples of the utility of incorporated beta-glucuronidase and antibodies onto the LPPC. The beta-glucuronidase can be used for the study of antigen-antibody interactions, whereas in studies with the antibody complex, we used anti-CD3 as an agonist to stimulate the proliferation of peripheral blood mononuclear cells via a receptor-mediated mechanism and anti-VEGFR for cell staining. In conclusion, the prepared LPPC can provide a platform to capture biologically and biochemically functional proteins on its surface for various applications, such as cell signaling, cell profiling, noncovalent enzyme-linked immunoassays, and others not mentioned. Biotechnol. Bioeng. Biotechnol. Bioeng. 2011; 108: 1318-1327. (C) 2010 Wiley Periodicals, Inc.
Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T cells
(2013-05-01)
Hsu, Wei-Tung
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Wu, Ming-Shiang
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Wu, Chang-Jer
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Chen, Chia-Hung
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Jian, Ting-Yan
Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T-cells associated with persistent infection
(2018-06-01)
Hsu, Wei-Tung
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Ho, Shu-Yi
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Jian, Ting-Yan
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Huang, Han-Ning
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Lin, Yu-Ling
Local Treg responses are involved in Helicobacter pylori-related inflammation and clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an important virulence factor associated with gastric carcinogenesis. This study to investigate the role of HpHSP60 in immunosuppression, particularly with regard to whether it could induce the production of Treg cells. For this purpose, human peripheral blood mononuclear cells (PBMCs) were treated with or without HpHSP60 in the presence of an anti-CD3 mAb to determine the effect of HpHSP60 on cell proliferation. In this report, HpHSP60 decreased the expression of CDK4 to significantly arrest the proliferation of mitogen-stimulated T-cells, which correlated with the induction of Treg cells. Moreover, monocytic cells were essential for the induction of HpHSP60-induced Treg cells via the secretion of IL-10 and TGF-beta after treatment with HpHSP60. Blockage of HpHSP60 with specific monoclonal antibodies significantly reduced the colonization of H. pylori and the expression of Treg cells in vivo. Overall, our results suggest that HpHSP60 could act on macrophages to trigger the expression of IL-10 and TGF-beta, thereby leading to an increase in Treg cells and inhibition of T-cell proliferation.
Inhibiting autophagy potentiates the antitumor efficacy ofEuphorbia royleanafor canine mammary gland tumors
(2020-06-12)
Huang, Yu-Ya
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Chen, Chia-Hung
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Hsu, Chia-Hui
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Kuo, Tsun-Yung
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Liu, Cheng-Chi
Background Canine mammary gland tumors (cMGTs) are the most common neoplasms in intact female canines and viewed as a suitable model for studying human breast cancers.Euphorbia royleanahas been reported to have a variety of antitumor efficacies. We have prepared the crude extracts ofE. royleanain ethanol and hexane solvents to evaluate the anti-tumor effects for cMGT in vitro and in vivo. Results The results showed thatE. royleanacould inhibit cell proliferation and colony formation in cMGT cells. The suppression of tumor cell growth resulted from necrosis and cell cycle arrest. Moreover, autophagy appears to play a critical role inE. royleana-mediated cell death by triggering cell apoptosis. The in vivo results also revealed thatE. royleanatreatment could reduce the size of solid tumors while exhibiting low toxicity in cMGT-bearing nude mice. Conclusions The anti-tumor mechanisms ofE. royleanawere firstly verified to show it would cause autophagic cell death, apoptosis, and cell cycle arrest in canine mammary tumor cells. The in vitro and in vivo findings in the present study revealedE. royleanahas potential anticancer effects for the treatment of canine mammary gland tumors.
Inhibition of breast cancer with transdermal tamoxifen-encapsulated lipoplex
(2016-02-19)
Lin, Yu-Ling
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Chen, Chia-Hung
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Wu, Hsin-Yi
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Tsai, Nu-Man
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Jian, Ting-Yan
Background: Tamoxifen is currently used for the treatment of both early and advanced estrogen receptor (ER) positive breast cancer in pre- and post-menopausal women. However, using tamoxifen routinely to inhibit endogenous or exogenous estrogen effects is occasionally difficult because of its potential side effects. Objectives: The aim of this study is to design a local drug delivery system to encapsulate tamoxifen for observing their efficacy of skin penetration, drug accumulation and cancer therapy. Methods: A cationic liposome-PEG-PEI complex (LPPC) was used as a carrier for the encapsulation of tamoxifen and forming 'LPPC/TAM' for transdermal release. The cytotoxicity of LPPC/TAM was analyzed by MTT. The skin penetration, tumor growth inhibition and organ damages were measured in xenograft mice following transdermal treatment. Results: LPPC/TAM had an average size less than 270 nm and a zeta-potential of approximately 40 mV. LPPC/TAM displayed dramatically increased the cytotoxic activity in all breast cancer cells, especially in ER-positive breast cancer cells. In vivo, LPPC drug delivery helped the fluorescent dye penetrating across the skim and accumulating rapidly in tumor area. Administration of LPPC/TAM by transdermal route inhibited about 86 % of tumor growth in mice bearing BT474 tumors. This local treatment of LPPC/TAM did not injury skin and any organs. Conclusion: LPPC-delivery system provided a better skin penetration and drug accumulation and therapeutic efficacy. Therefore, LPPC/TAM drug delivery maybe a useful transdermal tool of drugs utilization for breast cancer therapy.
Inhibitory Effects of Chloroform Extracts Derived from Corbicula fluminea on the Release of Pro-inflammatory Cytokines
(2012-04-25)
Lin, Ching-Min
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Lin, Yu-Ling
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Tsai, Nu-Man
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Wu, Hsin-Yi
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Ho, Shu-Yi
Corbicula fluminea, the primary freshwater bivalve cultivated in Taiwan, was formerly used as a remedy for hepatitis. Recent reports indicate that C. fluminea has many bioactivities, but it remains unknown whether C. fluminea affects inflammation. This study explored the anti-inflammatory activity of C.fluminea. C. fluminea was first treated with chloroform to obtain clam chloroform extracts (CCEs). On the basis of the assay for the release of pro-inflammatory cytokines in vitro and in vivo, the results show that the CCEs significantly lowered the release of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines. Additionally, the CCEs reduced LPS-induced organ damage. Real-time polymerase chain reaction analysis suggested that CCEs inhibit the LPS-induced mRNA expression of interleukin-1 beta and tumor necrosis factor-alpha. Western blot analysis indicated that the CCEs increased expression of I kappa B and attenuated the phosphorylation of I kappa B. Gas chromatography mass spectrometry suggests that phytosterols and fatty adds are responsible for the anti-inflammatory properties of CCEs. Taken together, CCEs have the potential to be developed as an anti-inflammatory functional food.
Lipo-PEG-PEI complex as an intracellular transporter for protein therapeutics
(2019-01-01)
Lin, Yu-Ling
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Chen, Chia-Hung
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Liu, Yen-Ku
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Huang, Tse-Hung
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Tsai, Nu-Man
Background: Protein or peptide drugs are emerging therapeutics for treating human diseases. However, current protein drugs are typically limited to acting on extracellular/cell membrane components associated with the diseases, while intracellular delivery of recombinant proteins replaces or replenishes faulty/missing proteins and remains inadequate. In this study, we developed a convenient and efficient intracellular protein delivery vehicle. Materials and methods: A cationic liposomal polyethylenimine and polyethylene glycol complex (LPPC) was developed to noncovalently capture proteins for protein transfer into cells via endocytosis. beta-glucuronidase (beta G) was used in vitro and in vivo as a model enzyme to demonstrate the enzymatic activity of the intracellular transport of a protein. Results: The endocytosed protein/LPPC complexes escaped from lysosomes, and the bound protein dissociated from LPPC in the cytosol. The enzymatic activity of beta G was well preserved after intracellular delivery in vitro and in vivo. Conclusion: Using LPPC as an intracellular protein transporter for protein therapeutics, we illustrated that LPPC may be an effective and convenient tool for studying diseases and developing therapeutics.
Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules
(2020-04-09)
Ho, Shu-Yi
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Chen, Pin-Rong
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Chen, Chia-Hung
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Tsai, Nu-Man
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Lin, Yu-Hsin
Background The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. Results LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. Conclusions The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.
Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch
(2012)
Chen, Chia-Hung
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Lin, Yu-Ling
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Liu, Yen-Ku
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He, Pei-Juin
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Lin, Ching-Min
The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab) isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig) A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC])-adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse-phagocytes. In contrast to Freund's adjuvant, LPPC preferentially activates-Th1-immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed Th2 immunities and high IgG1 serum titers. Taken together, the results demonstrate that the LPPC adjuvant not only increases the immunogenicity of antigens but also modulates host immunity to produce an appropriate Ab isotype by combining with immunomodulators.
Relationship between Energy Dosage and Apoptotic Cell Death by Modulated Electro-Hyperthermia
(2020-06-02)
Kao, Patrick Hung-Ju
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Chen, Chia-Hung
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Tsang, Yuk-Wah
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Lin, Chen-Si
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Chiang, Hsin-Chien
Modulated electro-hyperthermia (mEHT) is a form of mild hyperthermia (HT) used for cancer treatment. The principle utility of HT is the ability not only to increase cell temperature, but also to increase blood flow and associated pO(2) to the microenvironment. While investigational evidence has shown the unique ability of mEHT to elicit apoptosis in cancer cells, in vivo and in vitro, the same trait has not been observed with conventional HT. There is dissension as to what allows mEHT to elicit apoptosis despite heating to only mild temperatures, with the predominant opinion in favor of increased temperature at a cellular level as the driving force. For this study, we hypothesized that in addition to temperature, the amount of electrical energy delivered is a major factor in induction of apoptosis by mEHT. To evaluate the impact of electrical energy on apoptosis, we divided generally practiced mEHT treatment into 3 phases: Phase I (treatment start to 10min. mark): escalation from 25 degrees C to 37 degrees C Phase II (10min. mark to 15min. mark): escalation from 37 degrees C to 42 degrees C Phase III (15min. mark to 45min. mark): maintenance at 42 degrees C Combinations of mEHT at 18W power, mEHT at 7.5W power, water bath, and incubator were applied to each of the three phases. Power output was recorded per second and calculated as average power per second. Total number of corresponding Joules emitted per each experiment was also recorded. The biological effect of apoptotic cell death was assayed by annexin-V assay. In group where mEHT was applied for all three phases, apoptosis rate was measured at 31.18 +/- 1.47%. In group where mEHT was only applied in Phases II and III, apoptosis rate dropped to 20.2 +/- 2.1%. Where mEHT was only applied in Phase III, apoptosis was 6.4 +/- 1.7%. Interestingly, when mEHT was applied in Phases I and II, whether Phase III was conducted in either water bath at 42 degrees C or incubator at 37 degrees C, resulted in nearly identical apoptosis rates, 26 +/- 4.4% and 25.9 +/- 3.1%, respectively. These results showed that accumulation of mEHT at high-powered setting (18W/sec) during temperature escalation (Phase I and Phase II), significantly increased apoptosis of tested cancer cells. The data also showed that whereas apoptosis rate was significantly increased during temperature escalation by higher power (18W/sec), apoptosis was limited during temperature maintenance with lower power (7.5W/sec). This presents that neither maintenance of 42 degrees C nor accumulation of Joules by mEHT has immediate correlating effect on apoptosis rate. These findings may offer a basis for direction of clinical application of mEHT treatment.
Resistive switching behavior of sol-gel deposited TiO2 thin films under different heating ambience
(2013-09-01)
Lai, Chun-Hung
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Chen, Chia-Hung
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Tseng, Tseung-Yuen
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電子工程學系及電子研究所
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Department of Electronics Engineering and Institute of Electronics
We prepared anatase TiO2 films by sol-gel method under three thermal firing conditions to investigate the bipolar resistive switching (BRS) and unipolar resistive switching CURS) in Ag/TiO2/Pt structure. The devices are URS in an air atmosphere at 760 Torr, while those in an oxygen ambience at 1 Torr show BRS accompanying with forming-free and self-compliance. By examining the X-ray photoelectron spectroscopy (XPS) spectrum, different non-lattice oxygen content is observed. High concentration of oxygen vacancy is expected under oxygen-deficient treatment, and that would determine the electrode/oxide interface property and induce switching mode of polarity dependent or not. An improved performance of operation voltage dispersion down to 0.5 V and endurance up to 3000 cycles is obtained for those in reducing Ar. (C) 2012 Elsevier B.V. All rights reserved.
Specific drug delivery efficiently induced human breast tumor regression using a lipoplex by non-covalent association with anti-tumor antibodies
(2019-02-06)
Lin, Yu-Ling
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Tsai, Nu-Man
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Chen, Chia-Hung
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Liu, Yen-Ku
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Lee, Chung-Jen
BackgroundA cationic liposome-PEG-PEI complex (LPPC) was employed as a carrier for achieving targeted delivery of drug to human epidermal growth factor receptor-2 (HER2/neu)-expressing breast cancer cells. LPPC can be easily loaded with an anti-tumor drug and non-covalently associated with an anti-tumor antibody such as Herceptin that is clinically used to rapidly form immunoparticles within 1h.ResultsDrug-loaded LPPC have an average size about 250nm and a zeta potential of about 40mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280nm and the zeta potentials were about 23mV. Targeting ability of this delivery system was demonstrated through specific binding on surface of cells and IVIS images in vivo, which showed specific binding in HER2-positive SKBR3 cells as compared to HER2-negative Hs578T cells. Only the drug/LPPC/Herceptin complexes displayed dramatically increased the cytotoxic activity in cancer cells. Both in vitro and in vivo results indicated that Herceptin adsorbed on LPPC directed the immunocomplex towards HER2/neu-positive cells but not HER2/neu-negative cells. The complexes with either component (curcumin or doxorubicin) used in the LPPC-delivery system provided a better therapeutic efficacy compared to the drug treatment alone and other treatment groups, including clinical dosages of Herceptin and LipoDox, in a xenografted model.ConclusionsLPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.