簡易檢索 / 詳目顯示

回結果列表
研究生： 黎可莊
Jongjit Treekoon
論文名稱： 以不同形貌與結晶度之三氧化二釓奈米材料進行邊際效應標靶深層肺癌組織與核磁共振顯影引導放射性治療
Deep-Seated Lung Tumors Targeting Following Margination Effect Reveals Shape and Crystallinity Effects from Gd2O3 Nanoparticles for MR Imaging-Guided X-ray Therapy
指導教授： 葉晨聖
Yeh, Chen-Sheng
學位類別： 碩士
Master
系所名稱： 理學院 - 化學系
Department of Chemistry
論文出版年： 2021
畢業學年度： 109
語文別： 英文
論文頁數： 49
外文關鍵詞： Gadolinium oxide, Margination effect, X-rays, Crystallinity, Lung tumor
相關次數： 點閱：182  下載：0 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • The design of nanoparticles has a significant impact on the precise approach to lung deposition in the field of theranostic nanomedicine. In this work, three distinct shapes of biocompatible PEG-modified Gd2O3 nanoparticles were fabricated (scroll@PEG, oblate@PEG, and sphere@PEG) for MR imaging-guided X-ray therapy in deep-seated lung tumor. All Gd2O3 nanoparticles exhibited the effectiveness of T1 and T2 contrast agents with high proton relaxivities (r1 = 3.4-6.6 s-1mM-1 and r2 = 72.7-86.0 s-1mM-1) with different geometries showing greater values than the commercial and other Gd-based contrast agents. Amplification of electron generation induced DNA damage in lung cancer cells after X-rays exposure, which confirmed the radiotherapy efficacy of the three shapes and associated depending on their crystallinity. In the bloodstream, the geometrical effect of the non-spherical plate-like nanoparticles (scroll@PEG and oblate@PEG) serves as a great tumor-adhesion agent for the accumulation of lung via margination dynamics over the spherical nanoparticle (sphere@PEG). This study may provide a new strategy for designing nanoparticle shapes for lung tumor-targeted nanoparticles and regulating its crystallinity for X-ray stimulation cancer therapy.

    ABSTRACT I ACKNOWLEDGEMENTS II TABLE OF CONTENTS III LIST OF TABLES V LIST OF FIGURES VI CHAPTER ONE INTRODUCTION 1 1.1 Margination Dynamic for Enhanced Blood Circulation Time of Particles 1 1.2 The Important of Particle Shape for Vascular Wall Margination and Attachment 2 1.3 Margination Effect Applied in Micro-Nanomedicine 7 1.3.1 A Review of Particle Geometry Strategy to Overcome Barriers in Biomedical Application 7 1.3.2 Margination Effect for Enhanced the Lung Accumulation 10 1.4 Gadolinium-Based Nanoparticles MRI Contrast Agent and Radiosensitizer for Cancer Theragnostic 12 1.4.1 MRI Principles 12 1.4.2 Shape Matters: High Surface Area of Non-Spherical gadolinium oxide (Gd2O3) Nanoparticles Used for MRI Guided Cancer Therapy 13 1.4.3 Gadolinium Nanoparticles Have Been Developed as Radiosensitizers for Radiotherapy 14 CHAPTER TWO MOTIVATION 16 CHAPTER THREE RESEARCH DESIGN AND METHODOLOGY 18 3.1 Materials 18 3.2. Instruments 19 3.3. Research Methodology 21 CHAPTER FOUR RESULTS AND DISCUSSIONS 26 4.1 Characterization of Gd2O3 Nanoparticles (Scroll, Oblate, and Sphere) 26 4.2 In Vitro MR Imaging of PEG-Modified Gd2O3 at Different Geometries 31 4.3 Measurement of Hydroxyl Radicals Generation of PEG-modified Gd2O3 Nanoparticles 33 4.4 Stability Test of PEG-Modified Gd2O3 Nanoparticles in Different Solvents 35 4.5 Detection of DNA Double-Strand Breaks by PEG-Modified Gd2O3 Nanoparticles using Immunocytometry Assay 37 4.6 Cytotoxicity of PEG-Modified Gd2O3 Nanoparticles Without X-rays in Lung Cell Lines 39 4.7 In Vitro Microfluidic Chip Experiment of PEG-Modified Gd2O3 Nanoparticles with Various Shapes 40 4.8 Biodistribution of PEG-Modified Gd2O3 Nanoparticles in Major Organs 41 CHAPTER FIVE CONCLUSIONS 43 REFERENCES 44

    1. Min, Y.; Caster, J. M.; Eblan, M. J.; Wang, A. Z., Clinical translation of nanomedicine. Chem. Rev. 2015, 115 (19), 11147-11190.
    2. Yang, G.; Phua, S. Z. F.; Bindra, A. K.; Zhao, Y., Degradability and clearance of inorganic nanoparticles for biomedical applications. Adv. Mater. 2019, 31 (10), 1805730.
    3. Blanco, E.; Shen, H.; Ferrari, M., Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 2015, 33 (9), 941-951.
    4. Sen Gupta, A., Role of particle size, shape, and stiffness in design of intravascular drug delivery systems: insights from computations, experiments, and nature. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2016, 8 (2), 255-270.
    5. Decuzzi, P.; Lee, S.; Bhushan, B.; Ferrari, M., A Theoretical model for the margination of particles within blood vessels. Ann Biomed Eng 2005, 33 (2), 179-190.
    6. Gentile, F.; Chiappini, C.; Fine, D.; Bhavane, R. C.; Peluccio, M. S.; Cheng, M. M.; Liu, X.; Ferrari, M.; Decuzzi, P., The effect of shape on the margination dynamics of non-neutrally buoyant particles in two-dimensional shear flows. J Biomech 2008, 41 (10), 2312-8.
    7. Shah, S.; Liu, Y.; Hu, W.; Gao, J., Modeling particle shape-dependent dynamics in nanomedicine. J. Nanosci. Nanotechnol. 2011, 11 (2), 919-928.
    8. Liu, Y.; Tan, J.; Thomas, A.; Ou-Yang, D.; Muzykantov, V. R., The shape of things to come: importance of design in nanotechnology for drug delivery. Ther. Deliv. 2012, 3 (2), 181-194.
    9. Cooley, M.; Sarode, A.; Hoore, M.; Fedosov, D. A.; Mitragotri, S.; Sen Gupta, A., Influence of particle size and shape on their margination and wall-adhesion: implications in drug delivery vehicle design across nano-to-micro scale. Nanoscale 2018, 10 (32), 15350-15364.
    10. Tasciotti, E.; Liu, X.; Bhavane, R.; Plant, K.; Leonard, A. D.; Price, B. K.; Cheng, M. M.-C.; Decuzzi, P.; Tour, J. M.; Robertson, F.; Ferrari, M., Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nat. Nanotechnol. 2008, 3 (3), 151-157.
    11. Anselmo, A. C.; Modery-Pawlowski, C. L.; Menegatti, S.; Kumar, S.; Vogus, D. R.; Tian, L. L.; Chen, M.; Squires, T. M.; Sen Gupta, A.; Mitragotri, S., Platelet-like Nanoparticles: Mimicking Shape, Flexibility, and Surface Biology of Platelets To Target Vascular Injuries. ACS Nano 2014, 8 (11), 11243-11253.
    12. Massagué, J.; Obenauf, A. C., Metastatic colonization by circulating tumour cells. Nature 2016, 529 (7586), 298-306.
    13. Decuzzi, P.; Pasqualini, R.; Arap, W.; Ferrari, M., Intravascular delivery of particulate systems: does geometry really matter? Pharm Res 2009, 26 (1), 235-43.
    14. Decuzzi, P.; Godin, B.; Tanaka, T.; Lee, S. Y.; Chiappini, C.; Liu, X.; Ferrari, M., Size and shape effects in the biodistribution of intravascularly injected particles. J. Control. Release 2010, 141 (3), 320-7.
    15. Xu, R.; Zhang, G.; Mai, J.; Deng, X.; Segura-Ibarra, V.; Wu, S.; Shen, J.; Liu, H.; Hu, Z.; Chen, L.; Huang, Y.; Koay, E.; Huang, Y.; Liu, J.; Ensor, J. E.; Blanco, E.; Liu, X.; Ferrari, M.; Shen, H., An injectable nanoparticle generator enhances delivery of cancer therapeutics. Nat. Nanotechnol 2016, 34 (4), 414-8.
    16. Chiang, M.-R.; Su, Y.-L.; Chang, C.-Y.; Chang, C.-W.; Hu, S.-H., Lung metastasis-targeted donut-shaped nanostructures shuttled by the margination effect for the PolyDox generation-mediated penetrative delivery into deep tumors. Mater. Horiz. 2020, 7 (4), 1051-1061.
    17. Pautler, R. G., Mouse MRI: Concepts and Applications in Physiology. Physiology 2004, 19 (4), 168-175.
    18. Cao, Y.; Xu, L.; Kuang, Y.; Xiong, D.; Pei, R., Gadolinium-based nanoscale MRI contrast agents for tumor imaging. J. Mater. Chem. B 2017, 5 (19), 3431-3461.
    19. Wu, M.; Xue, Y.; Li, N.; Zhao, H.; Lei, B.; Wang, M.; Wang, J.; Luo, M.; Zhang, C.; Du, Y.; Yan, C., Tumor-microenvironment-induced degradation of ultrathin gadolinium oxide nanoscrolls for magnetic-resonance-imaging-monitored, activatable cancer chemotherapy. Angew. Chem. Int. Ed. 2019, 58 (21), 6880-6885.
    20. Collot, M.; Ashokkumar, P.; Anton, H.; Boutant, E.; Faklaris, O.; Galli, T.; Mély, Y.; Danglot, L.; Klymchenko, A. S., MemBright: A family of fluorescent membrane probes for advanced cellular imaging and neuroscience. Cell Chem. Biol. 2019, 26 (4), 600-614.e7.
    21. Liu, T.; Yang, K.; Liu, Z., Recent advances in functional nanomaterials for X-ray triggered cancer therapy. Prog. Nat 2020, 30 (5), 567-576.
    22. Sivasubramanian, M.; Chuang, Y. C.; Lo, L.-W., Evolution of nanoparticle-mediated photodynamic therapy: from superficial to deep-seated cancers. Molecules 2019, 24 (3), 520.
    23. Tamanoi, F.; Matsumoto, K.; Doan, T. L. H.; Shiro, A.; Saitoh, H., Studies on the exposure of gadolinium containing nanoparticles with monochromatic X-rays drive advances in radiation therapy. Nanomaterials (Basel) 2020, 10 (7), 1341.
    24. Hai, N. T. Q.; Anh, T. K.; Chau, P. T. M.; Ha, V. T. T.; Van Tuyen, H.; Huong, T. T.; Phuong, H. T.; Le Minh, Q., Multistep synthesis and upconversion luminescence of spherical Gd2O3:Er and Gd2O3:Er @ silica. J. Mater. Sci. Mater. Electron. 2020, 31 (4), 3354-3360.
    25. Park, S.; Baker, J. O.; Himmel, M. E.; Parilla, P. A.; Johnson, D. K., Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance. Biotechnol. Biofuels 2010, 3 (1), 10.
    26. Ahmad, M. Y.; Ahmad, M. W.; Yue, H.; Ho, S. L.; Park, J. A.; Jung, K.-H.; Cha, H.; Marasini, S.; Ghazanfari, A.; Liu, S.; Tegafaw, T.; Chae, K.-S.; Chang, Y.; Lee, G. H., In vivo positive magnetic resonance imaging applications of poly(methyl vinyl ether-alt-maleic acid)-coated ultra-small paramagnetic gadolinium oxide nanoparticles. Molecules 2020, 25 (5), 1159.
    27. Fang, J.; Chandrasekharan, P.; Liu, X.; Yang, Y.; Lv, Y.; Yang, C.-T.; Ding, J., Manipulating the surface coating of ultra-small Gd2O3 nanoparticles for improved T1-weighted MR imaging. Biomaterials 2014, 35 5, 1636-42.
    28. Louis, C.; Bazzi, R.; Flores, M. A.; Zheng, W.; Lebbou, K.; Tillement, O.; Mercier, B.; Dujardin, C.; Perriat, P., Synthesis and characterization of Gd2O3:Eu3+ phosphor nanoparticles by a sol-lyophilization technique. J. Solid State Chem. 2003, 173 (2), 335-341.
    29. Wu, C.; Cai, R.; Zhao, T.; Wu, L.; Zhang, L.; Jin, J.; Xu, L.; Li, P.; Li, T.; Zhang, M.; Du, F., Hyaluronic acid-functionalized gadolinium oxide nanoparticles for magnetic resonance imaging-guided radiotherapy of tumors. Nanoscale Res. Lett. 2020, 15 (1), 94.
    30. Yu, S.-M.; Cha, J.; Lee, J.-K., Synthesis of Eu3+-doped Gd2O3 in hollow nanoparticle structures by controlled chemical etching with poly(acrylic acid). RSC Advances 2013, 3 (37), 16374-16379.
    31. Park, J. Y.; Baek, M. J.; Choi, E. S.; Woo, S.; Kim, J. H.; Kim, T. J.; Jung, J. C.; Chae, K. S.; Chang, Y.; Lee, G. H., Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images. ACS Nano 2009, 3 (11), 3663-3669.
    32. Ahmad, M. W.; Kim, C. R.; Baeck, J. S.; Chang, Y.; Kim, T. J.; Bae, J. E.; Chae, K. S.; Lee, G. H., Bovine serum albumin (BSA) and cleaved-BSA conjugated ultrasmall Gd2O3 nanoparticles: Synthesis, characterization, and application to MRI contrast agents. Colloids Surf. A Physicochem. Eng. Asp. 2014, 450, 67-75.
    33. Gu, W.; Song, G.; Li, S.; Shao, C.; Yan, C.; Ye, L., Chlorotoxin-conjugated, PEGylated Gd2O3 nanoparticles as a glioma-specific magnetic resonance imaging contrast agent. RSC Advances 2014, 4 (91), 50254-50260.
    34. Ahrén, M.; Selegård, L.; Klasson, A.; Söderlind, F.; Abrikossova, N.; Skoglund, C.; Bengtsson, T.; Engström, M.; Käll, P.-O.; Uvdal, K., Synthesis and characterization of PEGylated Gd2O3 nanoparticles for MRI contrast enhancement. Langmuir 2010, 26 (8), 5753-5762.
    35. Ahrén, M.; Selegård, L.; Söderlind, F.; Linares, M.; Kauczor, J.; Norman, P.; Käll, P.-O.; Uvdal, K., A simple polyol-free synthesis route to Gd2O3 nanoparticles for MRI applications: an experimental and theoretical study. J. Nanoparticle Res. 2012, 14 (8), 1006.
    36. Das, G. K.; Heng, B. C.; Ng, S.-C.; White, T.; Loo, J. S. C.; D’Silva, L.; Padmanabhan, P.; Bhakoo, K. K.; Selvan, S. T.; Tan, T. T. Y., Gadolinium oxide ultranarrow nanorods as multimodal contrast agents for optical and magnetic resonance imaging. Langmuir 2010, 26 (11), 8959-8965.
    37. Strojan, K.; Leonardi, A.; Bregar, V. B.; Križaj, I.; Svete, J.; Pavlin, M., Dispersion of nanoparticles in different media importantly determines the composition of their protein corona. PLoS One 2017, 12 (1), e0169552-e0169552.
    38. Yu, S.-M.; Laromaine, A.; Roig, A., Enhanced stability of superparamagnetic iron oxide nanoparticles in biological media using a pH adjusted-BSA adsorption protocol. J. Nanoparticle Res. 2014, 16 (7), 2484.
    39. Moore, T. L.; Rodriguez-Lorenzo, L.; Hirsch, V.; Balog, S.; Urban, D.; Jud, C.; Rothen-Rutishauser, B.; Lattuada, M.; Petri-Fink, A., Nanoparticle colloidal stability in cell culture media and impact on cellular interactions. Chem. Soc. Rev. 2015, 44 (17), 6287-6305.
    40. Douglas, P.; Zhong, J.; Ye, R.; Moorhead, G. B.; Xu, X.; Lees-Miller, S. P., Protein phosphatase 6 interacts with the DNA-dependent protein kinase catalytic subunit and dephosphorylates gamma-H2AX. Nat. Rev. Mol. Cell Biol. 2010, 30 (6), 1368-81.

    下載圖示
    2026-08-08公開
    QR CODE