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논문 기본 정보

자료유형
학위논문
저자정보

이기욱 (경희대학교, 경희대학교 대학원)

지도교수
이상천, 정서영
발행연도
2018
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경희대학교 논문은 저작권에 의해 보호받습니다.

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이 논문의 연구 히스토리 (2)

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Cancer cells with an upregulated level of reactive oxygen species (ROS) are known to be susceptible to induction of intracellular oxidative stress. Therefore, elevating intracellular ROS production by exogenous ROS generators may be an efficient approach to selectively kill cancer cells. In this work, we aim to develop a Cu(II) arsenite-mineralized polymeric nanoparticle (CuAS-MNP) as a novel ROS amplifying anticancer drug. Upon endocytosis, the nanoparticles can increase the level of hydrogen peroxide (H2O2), and through the Fenton-like reaction, they can subsequently catalyze the conversion of H2O2 into highly toxic apoptosis-inducing hydroxyl radicals (·OH). CuAs minerals maintained its dormant crystalline structure at physiological pH, whereas, at endosomal pH, the release of Cu2+ ions and AS are coinstantaneously triggered by ionization of the CuAS minerals. This mineralized nano-Fenton reactor would serve as a novel oxidative stress amplifying system for effective cancer therapy.

목차

1. Introduction 1
2. Materials and methods 4
2.1. Materials 4
2.2 Synthesis of a poly(ethylene glycol)-b-poly(L-3,4-dihydroxy-L-phenylalanine) (PEG-PDOPA) copolymer 4
2.2.1. Synthesis of di-O,O''-acetyl-L-DOPA-N-carboxyanhydride ((AC2)-DOPA
-NCA) 4
2.2.2. Synthesis of PEG-b-PDOPA copolymer (PEG113-PDOPA8) 5
2.3. Preparation of Cu(HAsO3)-PMs 6
2.4. Characterization of CuAS-PMs 6
2.5. Serum stability of CuAS-PMs, PMs 7
2.6. Cytotoxicity of PMs, Cu-PMs, NiAS-PMs, CuAS-PMs 7
2.7. Evaluation of amplified ROS stress within cells 8
2.8. Apoptosis assay 8
3. Results and discussion 9
3.1. Preparation and characterization of PEG-b-PDOPA micelles 10
3.2. Characteristics of CuAS-PMs 13
3.3. pH-Contrilled release 20
3.4. In vitro evaluation of amplified ROS stress within MCF-7 cells 22
3.5. In vitro cytotoxicity of the PMs, Cu-PMs, free ATO, NiAS-PMs, CuAS-PMs 25
3.6. Apoptotic activity of CuAS-PMs 28
4. Conclusions 31
5. References 32

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