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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학위논문
- 저자정보
- 지도교수
- 정서영, 이상천
- 발행연도
- 2019
- 저작권
- 경희대학교 논문은 저작권에 의해 보호받습니다.
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이 논문의 연구 히스토리 (4)
2018
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초록· 키워드
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In contrast to normal cells, cancer cells have properties that upregulate the levels of reactive oxygen species (ROS). Hence, the selective elevation of the ROS level in MCF-7 cancer cells has been a promising approach for cancer treatment. The clinical success of arsenite in hematologic malignancies has not been reproduced in solid cancers due to poor pharmacokinetics and dose-limiting toxicity. To overcome these hurdles, we have designed a novel nanoparticulate formulation, in which medical compounds are encapsulated in mineralized nanoparticles. Herein, we aim to develop arsenite and L-buthionine sulfoximine (BSO) combined calcium carbonate (CaCO3) hybrid mineralized nanoparticles (MNPs) through the anionic block copolymer (poly(ethylene glycol-b-poly(L-aspartic acid)(PEG-PAsp))-templated mineralization that can not only release an inhibitor of ROS-scavenging antioxidants (BSO) but also release a ROS-generating agent (arsenite), thereby leading to amplification of oxidative stress in MCF-7 cancer cells and subsequent ROS-mediated apoptosis. The release of arsenite and BSO from As-BSO-CaCO3-MNPs would be effectively inhibited at physiological pH (pH 7.4), whereas, upon endocytosis (endosomal pH 5.0), the released arsenite would elevate the production level of hydrogen peroxide within MCF-7 cancer cells, while BSO would inhibit a critical step in glutathione synthesis, which synergistically enhances arsenite activity that inhibits MCF-7 cancer cell growth. Our mineralized nanoparticles that can modulate the ROS level may serve as an effective anticancer agent in terms of both efficacy and selectivity.
목차
1. Introduction 12. Materials and methods 52.1. Materials 52.2. Synthesis of PEG-b-PAsp block copolymer (PEG113-PAsp37) 52.3. Preparation of arsenite and L-Buthionine Sulfoximine loaded CaCO3 mineralized Nanoparticles (As-BSO-CaCO3-MNPs) through PEG-PAsp-templated mineralization 52.4. Characterization of As-BSO-CaCO3-MNPs 62.5. Serum stability of Arsenite-BSO-CaCO3-MNPs 62.6. Release profiles of Ca2+ ions, As and BSO from As-BSO-CaCO3-MNPs 72.7. Cytotoxicity of As-BSO-CaCO3-MNP 72.8. Evaluation of amplified ROS stress within MCF-7 cancer cells 72.9. Quantitative analysis of cellular drug uptake of As-BSO-CaCO3-MNPs 82.10. Visualization of As-BSO-CaCO3-MNPs cellular uptake and intracellular distribution 82.11. As-BSO-CaCO3-MNPs induced apoptosis in MCF-7 cells 92.12. Statistics 93. Results and discussion 103.1. Synthesis of PEG-b-PAsp block copolymer (PEG113-PAsp37) 103.2. Formation and characteristics of As-BSO-loaded CaCO3 mineralized nanoparticles 143.3. pH dependent release kinetic profiles of calcium ion, arsenite and BSO from As-BSO-CaCO3-MNPs 203.4. In vitro cytotoxicity of As-BSO-CaCO3-MNPs 233.5. Evaluation of amplified ROS generation within MCF-7 cells 283.6 Quantitative analysis of drug uptake of As-BSO-CaCO3-MNPs 303.7. Visualization of As-BSO-CaCO3-MNPs cellular uptake and intracellular distribution 323.8. As-BSO-CaCO3-MNPs induced apoptosis of MCF-7 cells 344. Conclusions 375. References 38
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