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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 牟中原(Chung-Yuan Mou) | |
dc.contributor.author | I-Ting Chien | en |
dc.contributor.author | 簡翊庭 | zh_TW |
dc.date.accessioned | 2021-07-11T15:03:19Z | - |
dc.date.available | 2022-08-26 | |
dc.date.copyright | 2019-08-26 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-16 | |
dc.identifier.citation | [1] Li, J., Shen, S., Kong, F., Jiang, T., Tang, C., & Yin, C. (2018). Effects of pore size on in vitro and in vivo anticancer efficacies of mesoporous silica nanoparticles. RSC Advances, 8(43), 24633-24640.
[2] Kresge, C. T., Leonowicz, M. E., Roth, W. J., Vartuli, J. C., & Beck, J. S. (1992). Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature, 359(6397), 710-712. [3] Yang, P., Gai, S., & Lin, J. (2012). Functionalized mesoporous silica materials for controlled drug delivery. Chemical Society Reviews, 41(9), 3679. [4] Narayan, R., Nayak, U., Raichur, A., & Garg, S. (2018). Mesoporous Silica Nanoparticles: A Comprehensive Review on Synthesis and Recent Advances. Pharmaceutics, 10(3), 118. [5] Chou, L. Y., Ming, K., & Chan, W. C. (2011). Strategies for the intracellular delivery of nanoparticles. Chem. Soc. Rev.,40(1), 233-245. [6] He, Q., Zhang, J., Shi, J., Zhu, Z., Zhang, L., Bu, W., . . . Chen, Y. (2010). The effect of PEGylation of mesoporous silica nanoparticles on nonspecific binding of serum proteins and cellular responses. Biomaterials, 31(6), 1085-1092. [7] Wu, S., Hung, Y., & Mou, C. (2011). Mesoporous silica nanoparticles as nanocarriers. Chemical Communications,47(36), 9972. [8] R. K. Iler, The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties, and Biochemistry, Wiley, New York, 1979. [9] Wu, S., & Mou, C. (2013). Synthesis of mesoporous silica nanoparticles. Chem. Soc. Rev., 42, 3862 [10] Yamada, H., & Urata, C. (2013). Preparation of aqueous colloidal mesostructured and mesoporous silica nanoparticles with controlled particle size in a very wide range from 20 nm to 700 nm. Nanoscale, 5(13), 6145. [11] 張雍,葉至誠 (2015)。雙離子性高分子材料界面之血液相容性質。化工,第 62 卷第 1 期 [12] Lu, F., Wu, S., & Hung, Y. (2009). Size Effect on Cell Uptake in Well-Suspended, Uniform Mesoporous Silica Nanoparticles. Small, 5(12), 1408-1413. [13] Cedervall, T., Lynch, I., & Dawson, K. A. (2007). Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proceedings of the National Academy of Sciences, 104(7), 2050-2055. [14] Vroman L, Adams A, Fischer GC, Munoz PC. Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces. Blood. 1980;55(1):156–159 [15] Hadjidemetriou, M., & Kostarelos, K. (2017). Evolution of the nanoparticle corona. Nature Nanotechnology, 12(4), 288-290. [16] Nguyen, V. H., & Lee, B. (2017). Protein corona: A new approach for nanomedicine design. International Journal of Nanomedicine, Volume 12, 3137-3151. [17] Docter, D., Westmeier, D., Markiewicz, M., Stolte, S., Knauer, S. K., & Stauber, R. H. (2015). ChemInform Abstract: The Nanoparticle Biomolecule Corona: Lessons Learned - Challenge Accepted? ChemInform, 46(42), 6094-6121. [18] Lynch I, Dawson KA. Protein-nanoparticle interactions. Nano Today. 2008;3(1):40–47. [19] Koegler, P., Clayton, A., & Kingshott, P. (2012). The influence of nanostructured materials on biointerfacial interactions. Advanced Drug Delivery Reviews, 64(15), 1820-1839. [20] Vertegel, A. A., Siegel, R. W., & Dordick, J. S. (2004). Silica Nanoparticle Size Influences the Structure and Enzymatic Activity of Adsorbed Lysozyme. Langmuir, 20(16), 6800-6807. [21] Hühn, D., Kantner, K., & Parak, W. J. (2013). Polymer-Coated Nanoparticles Interacting with Proteins and Cells: Focusing on the Sign of the Net Charge. ACS Nano, 7(4), 3253-3263. [22] Fleischer, C. C., & Payne, C. K. (2012). Nanoparticle Surface Charge Mediates the Cellular Receptors Used by Protein–Nanoparticle Complexes. The Journal of Physical Chemistry B, 116(30), 8901-8907. [23] Maiorano, G., Sabella, S., Sorce, B., Brunetti, V., Malvindi, M. A., Cingolani, R., & Pompa, P. P. (2010). Effects of Cell Culture Media on the Dynamic Formation of Protein−Nanoparticle Complexes and Influence on the Cellular Response. ACS Nano, 4(12), 7481-7491. [24] Nguyen, V. H., & Lee, B. (2017). Protein corona: A new approach for nanomedicine design. International Journal of Nanomedicine, Volume 12, 3137-3151. [25] Lundqvist, M., Sethson, I., & Jonsson, B. (2004). Protein Adsorption onto Silica Nanoparticles: Conformational Changes Depend on the Particles Curvature and the Protein Stability. Langmuir, 20(24), 10639-10647. [26] Tenzer, S., Docter, D., Rosfa, S., Wlodarski, A., Kuharev, J., Rekik, A., . . . Stauber, R. H. (2011). Nanoparticle Size Is a Critical Physicochemical Determinant of the Human Blood Plasma Corona: A Comprehensive Quantitative Proteomic Analysis. ACS Nano, 5(9), 7155-7167. [27] Gagner, J. E., Lopez, M. D., Dordick, J. S., & Siegel, R. W. (2011). Effect of gold nanoparticle morphology on adsorbed protein structure and function. Biomaterials, 32(29), 7241-7252. [28] Gessner, A., Waicz, R., Lieske, A., Paulke, B., Mäder, K., & Müller, R. (2000). Nanoparticles with decreasing surface hydrophobicities: Influence on plasma protein adsorption. International Journal of Pharmaceutics, 196(2), 245-249. [29] Hadjidemetriou, M., & Kostarelos, K. (2017). Evolution of the nanoparticle corona. Nature Nanotechnology, 12(4), 288-290. [30] Schöttler, S., Becker, G., Winzen, S., Steinbach, T., Mohr, K., Landfester, K., . . . Wurm, F. R. (2016). Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers. Nature Nanotechnology, 11(4), 372-377. [31] Bertrand, N., Grenier, P., Mahmoudi, M., Lima, E. M., Appel, E. A., Dormont, F., . . . Farokhzad, O. C. (2017). Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nature Communications, 8(1). [32] Ogawara, K., Furumoto, K., Nagayama, S., Minato, K., Higaki, K., Kai, T., & Kimura, T. (2004). Pre-coating with serum albumin reduces receptor-mediated hepatic disposition of polystyrene nanosphere: Implications for rational design of nanoparticles. Journal of Controlled Release, 100(3), 451-455. [33] Li, Z., Li, D., Li, Q., Luo, C., Li, J., Kou, L., . . . Sun, J. (2018). In situ low-immunogenic albumin-conjugating-corona guiding nanoparticles for tumor-targeting chemotherapy. Biomaterials Science, 6(10), 2681-2693. [34] Corbo, C., Molinaro, R., Taraballi, F., Furman, N. E., Hartman, K. A., Sherman, M. B., . . . Tasciotti, E. (2017). Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers. ACS Nano, 11(3), 3262-3273. [35] Oh, J. Y., Kim, H. S., Palanikumar, L., Go, E. M., Jana, B., Park, S. A., . . . Ryu, J. (2018). Cloaking nanoparticles with protein corona shield for targeted drug delivery. Nature Communications, 9(1). [36] Hadjidemetriou, M., Al-Ahmady, Z., Buggio, M., Swift, J., & Kostarelos, K. (2019). A novel scavenging tool for cancer biomarker discovery based on the blood-circulating nanoparticle protein corona. Biomaterials, 188, 118-129. [37] Dr. Liji Thomas, MD. (2018). Blood Plasma Components and Function. Retrieved from https://www.news-medical.net/health/Blood-Plasma-Components-and-Function.aspx (May 30, 2019) [38] Pathology Harmony group. (2011). Clinical Biochemistry Outcomes. [39] M. Schuchard, C. Melm, A. Crawford, H. Chapman, S. Cockrill, K. Ray, R. Mehigh, D. Chen, and G. Scott. (2005). Specifi c Depletion of Twenty High Abundance Proteins from Human Plasma. NCI Proteomic Technologies, 12-13. [40] Münzenberg, G. (2013). Development of mass spectrometers from Thomson and Aston to present. International Journal of Mass Spectrometry, 349-350, 9-18. [41] 台灣質譜學會 (2015)。第 2 章 游離法,質譜分析技術原理與應用,43-44 [42] Makarov, A. (2000). Electrostatic Axially Harmonic Orbital Trapping: A High-Performance Technique of Mass Analysis. Analytical Chemistry, 72(6), 1156-1162. [43] Scigelova, M., & Makarov, A. (2000). Fundamentals and Advances of Orbitrap Mass Spectrometry. Encyclopedia of Analytical Chemistry, 1-36. [44] Ingenuity Pathway Analysis (IPA) website. https://www.qiagenbioinformatics.com/products/ingenuity-pathway-analysis/ [45] Alison Motsinger-Reif. Introduction to Pathway and Network Analysis. Bioinformatics Research Center Department of Statistics North Carolina State University. [46] Matsumura, Y., and Maeda, H. (1986). A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46, 6387−92. [47] Abdalla, A. M., Xiao, L., Ullah, M. W., Yu, M., Ouyang, C., & Yang, G. (2018). Current Challenges of Cancer Anti-angiogenic Therapy and the Promise of Nanotherapeutics. Theranostics, 8(2), 533-548. [48] Inoue, S. (1989). Ultrastructure of Basement Membranes. International Review of Cytology, 57-98. [49] Danquah, M. K., Zhang, X. A., & Mahato, R. I. (2011). Extravasation of polymeric nanomedicines across tumor vasculature. Advanced Drug Delivery Reviews, 63(8), 623-639. [50] Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007). Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2(12), 751-760. [51] 曾嶸,賈偉平,吳家睿,謝佳輝,陳海冰,李榮霞,嚴中華。專利編號 CN10151400。上海: 中華人民共和國國家知識產權局。 [52] Ma, Y. J., Lee, B. L., & Garred, P. (2017). An overview of the synergy and crosstalk between pentraxins and collectins/ficolins: Their functional relevance in complement activation. Experimental & Molecular Medicine,49(4). [53] Palm, W., Park, Y., & Thompson, C. B. (2015). The Utilization of Extracellular Proteins as Nutrients Is Suppressed by mTORC1. Cell, 162(2), 259-270. Bertrand, N., Grenier, P., Mahmoudi, M., Lima, E. M., Appel, E. A., Dormont, F., . . . [54] Farokhzad, O. C. (2017). Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nature Communications, 8(1). [55] Unitport website. https://www.uniprot.org/. [56] Weiss, A. C., Kelly, H. G., Faria, M., Besford, Q. A., Wheatley, A. K., Ang, C., . . . Kent, S. J. (2019). Link between Low-Fouling and Stealth: A Whole Blood Biomolecular Corona and Cellular Association Analysis on Nanoengineered Particles. ACS Nano, 13(5), 4980-4991. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78548 | - |
dc.description.abstract | 中孔洞二氧化矽奈米材料在奈米生醫領域的應用上具有多功能的發展性,例如:標靶治療、顯影、追蹤等,然而當具有特定功能的奈米粒子進入生物系統時,大量的蛋白質吸附到奈米粒子表面,形成蛋白質冠冕,導致應用效果不如預期,因此了解這層介於奈米材料與生物體之間的蛋白質冠冕將有助於奈米生醫應用上的發展。
在我們的研究中,我們首先透過液相層析串聯質譜儀、熱重分析儀、動態光散色分析儀來鑑定奈米粒子在老鼠或人類血漿中蛋白質冠冕的成、吸附量多寡、以及表面電位的變化,並透過 ClueGo 和 IPA 進行代謝路徑分析,接著觀察蛋白質冠冕在 in vitro 及 in vivo 實驗結果上的影響,而後綜合上述實驗分析結果選出特定蛋白質:免疫球蛋白 G、富含組氨酸的糖蛋白、間-α-胰蛋白酶抑製劑重鏈 H4,運用這三種蛋白質將奈米粒子進行表面修飾,並注入進帶有腫瘤的動物模型中觀察蛋白質冠冕改變後奈米材料在生物系統內的高滲透長滯留效應及血液循環效果,研究結果顯示將材料進行蛋白質的表面修飾無法輕易的改善材料在生物體的應用性。 | zh_TW |
dc.description.abstract | Mesoporous Silica Nanoparticles (MSNs) have been developed for many biomedical purposes, such as targeted therapy and diagnostic system. However, once nanoparticles are exposed to the biological system, protein corona formed around the nanoparticles can result in unexpected outcome in terms of therapeutic efficiency, bio-distribution and pharmacokinetics. Therefore, understanding the composition as well as functionality of protein corona is crucial for nano-medicine development.
In our study, we use LC-MS/MS, SDS-PAGE, DLS and Zeta potential measurements to identify the protein corona after the in vitro incubation of nanoparticles with human plasma and in vivo injection of nanoparticles into the mice. Additional bio information were revealed by ClueGo and Ingenuity Pathway Analysis (IPA). According to the obtained information, we selected and conjugated three of the most prominent proteins including Immunoglobulin G, Histidine-rich glycoprotein and Inter-alpha trypsin inhibitor H4, to MSNs and exam their bio-distribution. Our results indicate the high tumor-targeting efficiency could be achieved more simply by reducing protein adsorption but not manipulating protein type on the surface of MSNs. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T15:03:19Z (GMT). No. of bitstreams: 1 ntu-108-R06223152-1.pdf: 12433952 bytes, checksum: 1f23f147f52aa5ba36df4d07ac39ee77 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 口試委員審定書 i
誌謝 ii 摘要 iii Abstract iv Contents v List of Figures ix List of Tables xiii Chapter 1 Introduction 1 1.1 Mesoporous Silica Nanoparticle 1 1.1.1 Synthesis of Mesoporous Silica Nanoparticle 2 1.2 Protein Corona 7 1.2.1 Structure and Composition of Corona 8 1.2.2 Protein Conformation 9 1.2.3 Parameters Affecting Protein Corona 10 1.2.4 Application of protein corona 12 1.3 Plasma Proteome 15 1.4 Introduction of Mass Spectrometry 16 1.4.1 Introduction to Mass Spectrometry 17 1.4.2 Electrospray Ionization 17 1.4.3 Mass Analysis System 19 1.4.4 High-Performance Liquid Chromatography 20 1.4.5 Liquid Chromatography Mass Spectrometry 21 1.5 Biological Pathway Analysis 22 1.6 Enhanced Permeability and Retention (EPR) effect 23 1.7 Motivations and Objectives 25 Chapter 2 Experimental section 27 2.1 Synthesis of Mesoporous Silica Nanoparticle 28 2.1.1 Characterization of mesoporous silica nanoparticle 29 2.2 Protein Conjugation of Nanoparticle 30 2.2.1 Synthesis of RMSN-PEG-PEI-IgG 30 2.2.2 Synthesis of RMSN-PEG-PEI-Ni with CRP/HRG/ITIH4 conjugation 31 2.3 Blood Sample Preparation 32 2.3.1 Human plasma 32 2.3.2 Mouse plamsa 32 2.4 Methods for Protein Corona Characterization 33 2.4.1 In vivo and in vitro protein corona formation and collection 33 2.4.2 Identification of protein corona composition by mass spectrometry 34 2.4.3 Protein corona analysis 36 2.4.4 TGA of protein corona 37 2.4.5 Drnamic light scattering (DLS) and zeta potential of protein corona 37 2.5 Western Blot 37 2.6 In Vitro experiment 38 2.6.1 Cell culture 38 2.6.2 Flow cytometry 38 2.7 In Vivo experiment 39 2.7.1 Bio-distribution and EPR effect 39 Chapter 3 Result and Discussion 40 3.1 Characterization of Mesoporous Silica Nanoparticle 40 3.1.1 Surface modification of 25 nm and 50 nm RMSN 40 3.1.2 25 nm RMSN-PEG-PEI-IgG 44 3.1.3 25 nm RMSN-PEG-PEI-Ni with CRP/HRG/ITIH4 conjugation 45 3.2 Characterization of In Vitro Protein Corona of 25 and 50 nm RMSN in Human Plasma 48 3.2.1 Physical characteristic of protein corona 48 3.2.2 Composition of protein corona 51 3.2.3 Basic analysis of protein corona 53 3.2.4 Pathway analysis by ClueGo 56 3.2.5 Pathway analysis by IPA 58 3.3 In Vitro experiment 62 3.3.1 Hela cell uptake 62 3.3.2 Macrophage cell uptake 63 3.3.3 Short conclusion for in vitro experiment and protein corona analysis result 65 3.4 Characterization of 25 nm RMSN In Vivo Protein Corona in Balb/c Plasma 67 3.4.1 Composition of protein corona 67 3.4.2 Basic analysis of protein corona 68 3.4.3 Pathway analysis by ClueGo 69 3.4.4 Pathway analysis by IPA 70 3.5 Western Blot and Mass Spectrometry Analysis for IgG pre-coating or conjugation 73 3.6 In Vivo experiment 77 3.6.1 EPR effect of RMSN 77 3.6.2 Bio-distribution and EPR effect of IgG pre-coating 25nm RMSN 78 3.6.3 Bio-distribution and EPR effect of 25nm RMSN-PEG-PEI-IgG 79 3.6.4 Bio-distribution and EPR effect of 25nm RMSN-PEG-PEI-Ni with CRP/ ITIH4 conjugation 80 Chapter 4 Conclusion 82 Reference 84 | |
dc.language.iso | en | |
dc.title | 中孔洞二氧化矽奈米材料的特性與其蛋白質冠冕在奈米材料與生物系統上交互作用的影響 | zh_TW |
dc.title | Effect of Mesoporous Silica Nanoparticle Properties and Associated Protein Corona on Nano-Bio Interactions | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 徐丞志(Cheng-Chih Hsu),葉晨聖(Chen-Sheng Yeh),胡尚秀(Shang-Hsiu Hu) | |
dc.subject.keyword | 中孔洞二氧化矽奈米材料,蛋白質冠冕,高滲透長滯留效應,液相層析串聯質譜儀,免疫球蛋白 G,富含組氨酸的糖蛋白,間-α-胰蛋白?抑製劑重鏈 H4, | zh_TW |
dc.subject.keyword | Mesoporous Silica Nanoparticle,Protein Corona,EPR effect,LC-MS/MS,ClueGo,IPA,IgG,HRG,ITIH4, | en |
dc.relation.page | 90 | |
dc.identifier.doi | 10.6342/NTU201900025 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-08-16 | |
dc.contributor.author-college | 理學院 | zh_TW |
dc.contributor.author-dept | 化學研究所 | zh_TW |
顯示於系所單位: | 化學系 |
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