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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林文澧(Win-Li Lin) | |
| dc.contributor.author | Chung-Yin Lin | en |
| dc.contributor.author | 林中英 | zh_TW |
| dc.date.accessioned | 2021-06-15T05:11:37Z | - |
| dc.date.available | 2012-07-28 | |
| dc.date.copyright | 2010-07-28 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-07-23 | |
| dc.identifier.citation | [1] Su CH, Chang CY, Wang HH, Wu YJ, Bettinger T, Tsai CH, Yeh HI. Ultrasounic microbubble-mediated gene delivery causes phenotypic changes of human aortic endothelial cells. Ultrasound Med Biol 2010;36:449-458.
[2] Fukumura D, Jain RK. Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. Microvasc Res 2007;74:72-84. [3] Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182-1186. [4] Garrel D. A natural liquid cartilage extract brings new hope for patients with metastatic renal cell carcinoma. Townsend Letter for Doctors and Patients Jan, 2004. [5] Lunt SJ, Kalliomaki TMK, Brown A, Yang VX, Milosevic M, Hill RP. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours. BMC Cancer 2008;8:1-14. [6] Boxter LT, Jain RK. Transport of fluid and macromolecules in tumors I. role of interstitial pressure and convection. Microvasc Res 1989;37:77-104. [7] Nathan SS, Gasas-Ganem JE, Yang R, Kawano H, Sowers R, Diresta GR, Kolb AE, Huvos AG, Gorlick R, Healey JH. Angiogenesis in osteosarcoma is regulated by tumor interstitial fluid pressure. Proc Amer Assoc Cancer Res 2005;46. [8] Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis 2000;21:505-515. [9] Folkman J. Anit-angiogenesis: new concept for therapy of solid tumors. Ann Surg 1972; 175:409-416. [10] Truskey GA, Yuan F, Katz DF. Trasnport phenomena in biological systems. Pearson Prentice Hall: New Jersey, Chap 15, 2004. [11] Roberts WG, Palade GE. Neovasculature induced by vascular endothelial factor is fenestrated. Cancer Res 1997;57:765-772. [12] Brannon-Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Delivery Rev 2009;61:364. [13] Zhang H, Yee D, Wang C. Quantum dots for cancer diagnosis and therapy: biological and clinical perspectives. Nanomedicine 2008;3:83-91. [14] Jain KK. Application of nanobiotechnology in clinical diagnostics, Clin Chem 2007;53:2002-2009. [15] Schroeder JE, Shweky, Shmeeda IH, Banin U, Gabizon A. Folate-mediated tumor cell uptake of quantum dots entrapped in lipid nanoparticles, J Control Release 2007;124:28-34. [16] Rhyner MN, Smith AM, Gao X, Mao H, Yang L, Nie S. Quantum dots and multifunctional nanoparticles: new contrast agents for tumor imaging, Nanomedicine 2006;1:209-217. [17] Derfus AM, Chan WCW, Bhatia SN. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 2004;4:11-18. [18] Kim S, Lim YT, Soltesz EG, Grand AMD, Lee J, Nakayama A, Parker JA, Mihaljevic T, Laurence RG, Dor DM, Cohn LH, Bawendi MG, Frangioni JV. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 2004;22:93-97. [19] Ballou B, Ernst LA, Andreko S, Harper T, Fitzpatrick JAJ, Waggoner AS, Bruchez MP. Sentinel lymph node imaging using quantum dots in mouse tumor models. Bioconjug Chem 2007;18:389-396. [20] Larson DR, Zipfel WR, Williams RM, Clark SW, Bruchez MP, Wise FW, Webb WW. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 2003;300:1434-436. [21] Duertret B, Skourides P, Norris DJ, Noireaux V, Brivanlou AH, Libchaber A. In vivo imaging of quantum dots encapsulated in phosphorlipid micelles. Science 2002;298:1759-1762. [22] Peer D, Karp JM, Hong S, Farokhazd OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Biotechnol 2007;2:751-760. [23] Staples BJ, Roeder BL, Husseini GA, Badamjav O, Schaalje GB, Pitt WG. Role of frequency and mechanical index in ultrasonic-enhanced chemotherapy in rats. Cancer Chemother pharmacol 2009;64:593-600. [24] Tiera MJ, Winnik FM, Fernandes JC. Synthetic and natural polycations for gene therapy: State of the art and new perspectives. Current Gene Therapy 2006;6:59-71. [25] Goss SA, Johnston RL, Dunn F. Comprehensive compilation of empirical ultrasonic properties of mammalian tissues, J Acoust Soc Am 1978;64:423-453. [26] Nyborg WL. Biological effects of ultrasound: Development of safety guidelines. Part ii: General review. Ultrasound Med Biol 2001;27:301-333. [27] Feril LB, Kondo T, Zhao QL, Ogawa R. Enhancement of hyperthermia-induced apoptosis by non-thermal effects of ultrasound. Cancer Lett 2002;178:63-70. [28] Tachibana K, Uchida T, Ogawa K, yamashita N, Tamura K. Induction of cell-membrane porosity by ultrasound. Lancet 1999;353:1409. [29] Rooney JA. Hemolysis near an ultrasonically pulsating gas bubble. Science 1970;169:869-871. [30] Church CC. Frequency, pulse length, and the mechanical index. Acoust Res Lett Online 2005;6:162-168. [31] Kong G, Dewhirst MW. Hyperthermia and liposomes: a review. Int J Hyperthermia 1999;15: 345–370. [32] Lindner JR. Micro bubbles in medical imaging: current applications and future directions. Nat Rev Drug Discov 2004;3:527-532. [33] Mansur HS. Quantum dots and nanocomposities. WIRES Nanomed Nanobiotechnol 2010;2:113-129. [34] Yelin D, Silberberg Y. Laser scanning third-harmonic-generation microscopy in biology. Optics Express 1999;5:169-175. [35] Liu TM, Chan MC, Chen IH, Chia SH, Sun CK. Miniaturized multiphoton microscope with 24Hz frame-rate. Optics Express 2008;16:10501-10506. [36] Lippitz M, van Dijk MA, Orrit M. Third-harmonic generation from single gold nanoparticles. Nano Lett 2005;5:799-802. [37] Bergers G, Benjamin LE. Tumorgenesis and the angiogenic switch. Nat Rev Cancer 2003;3:401-410. [38] Jain RK. 1995 Whitaker Lecture: delivery of molecules, particles, and cells to solid tumors. Ann Biomed Eng 1996;24:457-473. [39] Boucher Y, Baxter LT, Jain RK. Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy. Cancer Res 1990;50:4478-4484. [40] Rapoport N, Pitt WG, Sun H, Nelson JL. Drug delivery in polymeric micelles: from in vitro to in vivo. J Control Release 2003;91:85-95. [41] Peng CL, Lai PS, Lin FH, Wu YH, Shieh MJ. Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer xenograft model using SN-38-loaded chlorine-core block copolymer micelles. Biomaterials 2009;30:3614-3625. [42] Leunig M, Goetz AE, Delliam M, Zetterer G, Gamarra F, Jain RK, Messmer K. Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response. Cancer Res 1992;52:487-490. [43] Kong G, Braun RD, Dewhirst MW. Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size. Cancer Res 2000;60:4440-4445. [44] Dreher MR, Liu W, Michelich CR, Dewhirst MW, Chilkoti A. Thermal cycling enhances the accumulation of a temperature-sensitive biopolymer in solid tumors Cancer Res 2007;67:4418-4424. [45] Schlicher RK, Radhakrishna H, Tolentino TP, Apkarian RP, Zarnitsyn V, Prausnitz MR. Mechanism of intracellular delivery by acoustic cavitation. Ultrasound Med Biol 2006;32:915-924. [46] Husseini GA, Pitt WG. The use of ultrasound and micelles in cancer treatment. J Nanosci Nanotechnol 2008;8:2205-2215. [47] Price RJ, Skyba DM, Kaul S, Skalak TC. Delivery of colloidal particles and read blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound. Circulation 1998;98:1264-1267. [48] Rapoport NY, Kennedy AM, Shea JE, Scaife CL, Nam KH. Controlled and targeted tumor chemotherapy by ultrasound-activated nanoemulsions/ microbubbles. J Control Release 2009;138:268-276. [49] Ellegala DB, Leong-Poi H, Carpenter JE, Klibanov AL, Kaul S, Shaffrey ME, Sklenar J, Lindner JR. Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to αvβ3 . Circulation 2003;108:336-341. [50] Netti PA, Baxter LT, Boucher Y, Skalak R, Jain RK. Time-dependent behaviour of interstitial fluid pressure in solid tumors: implications for drug delivery. Cancer Res 1995;55:5451-5458. [51] Salnikov AV, Inversen VV, Koisti M, Sundberg C, Johansson L, Stuhr LB,Sjoquist M, Ahlstrom H, Reed RK, Rubin K. Lowering of tumor interstitial fluid pressure specifically augments efficacy of chemotherapy. FASEB J 2003;17:1756-758. [52] Shieh MJ, Peng CL, Lou PJ, Chiu CH, Tsai TY, Hsu CY, Yeh CY, Lai PS. Non-toxic phototriggered gene transfection by PAMAM-porphyrin conjugates. J Control Release 2008;129:200-206. [53] Wolinsky JB, Grinstaff MW. Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv Drug Deliver Rev 2008;60:1037-1055. [54] Mikhail AS, Allen C. Block copolymer micelles for delivery of cancer therapy: Transport at the whole body, tissue and cellular levels. J Control Release 2009;138:214-23. [55] Dreher MR, Liu W, Michelich CR, Dewhirst MW, Yuan F, Chikoti A. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst 2006;98:335-344. [56] Liu Y, Miyoshi H, Nakamura M. Nanomedicine for drug delivery and imaging: a promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. Int J Cancer 2007;120:2527-2537. [57] Jain R, Dandekar P, Patravale V. Diagnostic nanocarriers for sentinel lymph node imaging. J Control Release 2009;138:90-102. [58] Schroeder JE, Shweky I, Shmeeda H, Banin U, Gabizon A. Folate-mediated tumor cell uptake of quantum dots entrapped in lipid nanoparticles. J Control Release 2007;124:28-34. [59] Rhyner MN, Smith AM, Gao X, Mao H, Yang L, Nie S. Quantum dots and multifunctional nanoparticles: new contrast agents for tumor imaging. Nanomedicine 2006;1:209-217. [60] Bothun GD, Rabideau AE, Stoner MA. Hepatoma cell uptake of cationicmultifluorescent quantum dot liposomes. J Phys Chem B 2009;113:7725-7728. [61] Chang CF, Chen CY, Chang FH, Tai SP, Chen CY, Yu CH, Tseng YB, ILiu LS, Su WF, Sun CK. Quantum dots for cancer diagnosis and therapy: biological and clinical perspectives. Opt Express 2008;16:9534-9548. [62] Carion O, Mahler B, Pons T, Dubertret B. Synthesis, encapsulation, purification and coupling of single quantum dots in phospholipid micelles for their use in cellular and in vivo imaging. Nat Protocols 2007;2:2383-2390. [63] Majetich SA, Carter AC. Surface effects on the optical-properties of cadmium selenide quantum dots. J Phy Chem 1993;97:8727-8737. [64] Lukyanov AN, Gao Z, Mazzola L, Torchilin VP. Polyethylene glycol-diacyllipid micelles demonstrate increased acculumation in subcutaneous tumors in mice. Pharm Res 2002;19:1424-1429. [65] Bradford MM. A rapid and sensitive methods for quantification of microgram quantities of protein utilizing the principle for protein-dye binding. Anal Biochem 1976;7:248-254. [66] Rychak JJ, Lindner JR, Ley K, Klibanov AL. Deformable gas-filled microbubbles targeted to P-selectin. J Control Release 2006;114:288-299. [67] Rychak JJ, Klibanov AL, Hossack JA. Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: in vitro verification. IEEE Trans Ultrason Ferroelectr Freq Cont rol 2005;52:421-433. [68] Hartwell DW, Butterfield CE, Frenette PS, Kenyon BM, Hynes RO, Folkman J, Wagner DD. Angiogenesis in P- and E-Selectin-deficient mice. Microcirculation 1998;5:173-178. [69] Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353-364. [70] Bekeredjian R, Kroll RD, Fein E, Tinkov S, Coester C, Winter G, Katus HA, Kulaksiz H. Ultrasound targeted microbubble destruction increases capillary permeability in hepatomas. Ultrasound Med Biol 2007;33:1592-598. [71] Fisher NG, Christiansen JP, Klibanov A, Taylor RP, Kaul S, Lindner JR. Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement. J Am Coll Cardiol 2002;26:1340-1347. [72] Gerstner ER, Sorensen AG, Jain RK, Batchelor TT. Advances in neuroimaging techniques for the evaluation of tumor growth, vascular permeability, and angiogenesis in gliomas. Curr Opin Neurol 2008;21:728-735. [73] Netti PA, Baxter LT, Boucher Y, Skalak R, Jain RK. Time-dependent behavior of interstitial fluid pressure in solid tumors : implications for drug delivery. Cancer Res 1995;55:5451-5458. [74] Crowder KC, Hughes MS, Marsh JN, Barbieri AM, Fuhrhop RW, Lanza GM, Wickline SA. Sonic activation of molecularly-target ed nanoparticles accelerates transmembrane lipid delivery to cancer cells through cont act-medicated mechanisms: implications for enhanced local drug delivery. Ultr asound Med Biol 2005;31:1693-1700. [75] Liu Y, Miyoshi H, Nakamura M. Nanomedicine for drug delivery and imaging: a promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. Int J Cancer 2007;120:2527-2537. [76] Rapoport NY, Kennedy AM, Shea JE, Scaife CL, Nam KH. Controlled and targeted tumor chemotherapy by ultrasound-activated nanoemulsions/ microbubbles. J Control Release 2009;138:268-276. [77] Schlicher RK, Radhakrishna H, Tolentino TP, Apkarian RP, Zarnitsyn V, Prausnitz MR. Mechanism of intracellular delivery by acoustic cavitation. Ultrasound Med Biol 2006;32:915-924. [78] Hancock HA, Smith LH, Cuesta J, Durrani AK, Angstadt M, Palmeri ML, Kimmel E, Frenkel V. Investigations into pulsed high-intensity focused ultrasound-enhanced delivery: preliminary evidence for a novel mechanism. Ultrasound Med Biol 2009;35:1722-1736. [79] Husseini GA, Pitt WG. Micelles and nanoparticles for ultrasonic drug and gene delivery. Adv Drug Deliv Rev 2008;60;1137-1152. [80] Ng KY, Liu Y. Therapeutic ultrasound: its application in drug delivery. Med Res Rev 2002;22:204-223. [81] Bothun GD, Rabideau AE, Stoner MA. Hepatoma cell uptake of cationic multi- fluorescent quantum dot liposomes. J Phys Chem B 2009;113:7725-7728. [82] Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 2001;220:640-646. [83] McDannold N, Vykhodtseva N, Hynynen K. Effects of acoustic parameters and ultrasound contrast agent dose on focused-ultrasound i nduced blood-brain barrier disruption. Ultrasound Med Biol 2008;34:930-938. [84] Morel D, Schwieger I, Hohn, L, Terrettaz J, Llull, JB, Cornioley, YA, Schneider M. Human pharmacokinetics and safety evaluation of SonoVue TM , a new contrast agent for ultrasound imaging. Inves Radiol 2001;35:80-90. [85] Aoyagi T, Ishikawa H, Miyaji K, Hayakawa K, Hata M. Cadmium-induced testiculardamage in a rat model of subchronic intoxication. Reprod Med Biol 2002;1:59-63. [86] Tang XL, Peng XH, Dou W, Mao J, Zheng JR, Qin WW, Liu WS, Chang J, Yao XJ. Design of a semirigid molecule as a selective fluorescent chemosensor for recognition of Cd(II). Org Lett 2008;10: 3653-56. [87] Hernot S, Klibanov AL. Microbubbles in ultrasound-triggered drug and gene delivery. Adv Drug Deliv Rev 2008;60:1153-1166. [88] Hynynen K. Macromolecular delivery across the blood-brain barrier. Methods Mol Biol 2009;480:175-185. [89] Frenkel V. Ultrasound mediated delivery of drugs and genes to solid tumors. Adv Drug Deliver Rev 2008;60:1193-208. [90] Kinoshita M, McDannold N, Jolesz FA, Hynynen K. Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption, Proc Natl Acad Sci 2006;103:11719-11723. [91] Yang FY, Fu WM, Chen WS, Yeh WL, Lin WL. Quantitative evaluation of the use of microbubbles with transcranial focused ultrasound on blood-brain-barrier disruption. Ultrason Sonochem 2008;15:636-43. [92] Diederich CJ, Hynynen K. Ultrasound technology for hyperthermia, Ultrasound Med Bio 1999;25:871-887 [93] Treat LH, McDannold N, Vykhodtseva N, Zhang Y, Tam K, Hynynen K. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound Int J Cancer 2007;121:901-907. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46487 | - |
| dc.description.abstract | 本研究目標，是以「非侵入式療法」為立基，利用「超音波」與「微氣泡」，搭配奈米顆粒之使用，促使微血管產生破裂及組織微環境變化，以達「區域性釋放」之效果，強化藥物有效地進入腫瘤組織並增加細胞對藥物之吸收，來大幅提昇藥物之治療效果，及降低其對人體其他正常組織之副作用。
本研究是利用聚焦型超音波及微氣泡來強化奈米顆粒釋放至腫瘤組織累積之定量與定性及最佳參數做深入研究探討。將皮下荷腫瘤Balb/c 小白鼠利用尾靜脈先注射微氣泡(SonoVue®)後，立即施打超音波(操作頻率為1-MHz；峰值聲壓1.2-MPa)，之後經由尾靜脈分別注射4種不同大小之脂質披覆量子點奈米顆粒(30到180 nm)，施打完超音波後約24小時，取下腫瘤組織，隨後透過石墨爐式原子吸收光譜儀、光激發螢光頻譜，和倍頻分子影像顯微鏡對控制組與實驗組分別進行脂質披覆量子點奈米顆粒的定量與定性分析。隨後進一步利用免疫轉印法來分析血管破裂後表現於組織內的生化標誌─P-selectin蛋白質。 本研究亦探討：微氣泡之劑量、超音波震盪時間、治療程序對奈米顆粒在腫瘤組織累積量的影響及奈米顆粒在腫瘤組織中累積隨時間變化，另外亦探討治療後之腫瘤組織再次施打超音波來強化奈米顆粒 之累積量。 由實驗結果可知，聚焦型超音波結合30 uL/kg劑量的微氣泡，能提升腫瘤組織內之奈米顆粒累積，其30、80、130與180 nm奈米顆粒經分析後，在腫瘤組織裡的含量分別為4.47、2.27、0.99與0.82 (ug Cd)/(g tumor); 而不施用微氣泡的對照組，其累積量分別只有1.12、0.75、 0.26與 0.34 (ug Cd)/(g tumor)。在相同的條件下，越小顆粒的奈米粒子在組織內有較高的累積量。再者，免疫轉印法進一步驗證了聚焦型超音波能引起微氣泡震盪/破壞，致使血管壁破裂，使得血管滲透性增加，提升奈米顆粒在腫瘤組織裡的累積。研究結果顯示聚焦型超音波結合微氣泡是一有前瞻性的方法，能促使奈米顆粒有效地進入腫瘤組織內，施打超音波時間之長短與微氣泡之劑量是強化奈米顆粒進入腫瘤組織的最重要因素。 | zh_TW |
| dc.description.abstract | Ultrasound-enhanced drug delivery system is a promising technique for noninvasive cancer treatment. Ultrasound-mediated microbubble destruction may enhance the release of nanoparticles from vasculature to tumor tissues. In this study, we used four different sizes of lipid-coated CdSe quantum dot (LQD) nanoparticles ranging from 30 to 180 nm, 1.0-MHz pulsed focused ultrasound (FUS) with a peak acoustic pressure of 1.2-MPa, and an ultrasound contrast agent (UCA; SonoVue®) at a dose of 30 uL/kg to investigate any enhancement of targeted delivery. Tumor-bearing male Balb/c mice were first injected with UCA intravenously, were then sonicated at the tumors with FUS, and were finally injected with 50 uL of the LQD solution after the sonication. The mice were sacrificed about 24 hr after the sonication, and then we quantitatively and qualitatively evaluated the deposition of LQDs in the tumors by using graphite furnace atomic absorption spectrometry (GF-AAS), photoluminescence spectrometry (PL), and harmonic generation microscopy (HGM). Further, immunoblotting analysis served to identify the biochemical markers reflecting the vascular rupture. The experimental results show that the amount of LQDs deposited in tumor tissues was greater in cases of FUS/UCA application, especially for smaller LQDs, being 4.47, 2.27, 0.99, and 0.82 (ug Cd)/(g tumor) for 30, 80, 130, and 180 nm of LQDs, respectively; compared to 1.12, 0.75, 0.26, and 0.34 (ug Cd)/(g tumor) in absence of FUS/UCA. The immunoblotting analysis further indicates that FUS-induced UCA oscillation/destruction results in rupture areas in blood vessels increasing the vascular permeability and thus justifying for the higher quantity of nanoparticles deposited in tumors.
Furthermore, we studied the effects of the injected UCA dose (0-300 uL/kg), FUS sonication duration (0-300 sec), and treatment-procedure sequence on the accumulation of nanoparticles in the tumors 24 hr after the treatment, and the time response of the accumulation (0.5-24 hr). After the treatment, the mice were sacrificed and perfused, and then the tumor tissues were harvested for quantifying the amount of nanoparticles using graphite furnace atomic absorption spectrometry (GF-AAS). The results showed that pulsed-FUS sonication with UCA can effectively enhance the vascular permeability for LQD nanoparticle delivery into the sonicated tumors. It indicates that this technique is promising for a better nanodrug delivery for tumor chemotherapy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T05:11:37Z (GMT). No. of bitstreams: 1 ntu-99-D95548010-1.pdf: 3113955 bytes, checksum: 50da3d6e924a19091e2376efd9a186c1 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
ACKNOWLEDGEMENTS ii 中文摘要 iii ABSTRACT v TABLE OF CONTENTS vii LIST OF TABLES xi LIST OF FIGURES xii CHAPTER 1 INTRODUCTION 1 1.1 Overview 1 1.2 Thesis outline 2 1.3 Background 3 1.3.1 Characteristics of tumor’s angiogenesis 3 1.3.2 Enhanced permeability and retention (EPR) effect in tumors 5 1.3.3 Nanoparticles 7 1.3.3.1 Quantum dot (QD) nanoparticles 8 1.3.3.2 Lipid-coated quantum dot nanoparticles (LQDs) 9 1.3.4 Ultrasound sonication 10 1.3.4.1 High intensity focused ultrasound (HIFU) 13 1.3.4.2 Hyperthermia 14 1.3.4.3 Ultrasound contrast agnet (UCA); Microbubbles (MBs) 14 1.3.4.4 Ultrasound sonciation with microbubbles in nanoparticle delivery 15 1.3.5 Spectrometry 17 1.3.5.1 Graphite furnace atomic absorption spectrometry (GF-AAS) 18 1.3.5.2 Photoluminescence spectrometry (PL) 19 1.3.5.3 Harmonic generation microscopy (HGM) 20 1.4 Objective 24 CHAPTER 2 QUANTITATIVE AND QUALITATIVE INVESTIGATION INTO THE IMPACT OF FOCUSED ULTRASOUND WITH MICROBUBBLE ON THE DELIVERY 26 2.1Methodology 31 2.1.1 Materials 31 2.1.2 Synthesis of cadmium-selenide quantum dots (QDs) and lipid-coated CdSe quantum dot nanoparticles (LQDs) 32 2.1.2.1 The particle sizes of LQD nanoparticles 36 2.1.2.2 The photoluminescence (PL) of QDs and LQD nanoparticles 36 2.1.2.3 The morphology of QDs and LQD nanoparticles 36 2.1.3 Cell culture 37 2.1.4 In vivo animal model 38 2.1.5 Ultrasound system 39 2.1.6 Experimental procedure 42 2.1.7 Quantitative determination of cadmium accumulation in tumor tissue with graphite furnace atomic absorption spectrometry (GF-AAS) 43 2.1.8 Qualitative analysis of LQDs with photoluminescence spectrometry (PL) 43 2.1.9 Deposition analysis of LQDs with optical harmonic generation microscopy (HGM) 44 2.1.10 Determination of blood-vessel rupture with P- selectin expression 47 2.1.10.1 SDS-PAGE and western blotting 47 2.1.11 Temperature measurement 47 2.1.12 Statistical analysis 48 2.2 Results and discussion 49 2.2.1 Characterization of lipid-coated quantum dot nanoparticles (LQDs) 49 2.2.2 Enhancement of LQDs’ extravasation by ultrasound sonication with microbubbles 51 2.2.3 Optical imaging analysis of LQDs’ release enhanced by ultrasound sonication with microbubbles 54 2.2.4 Blood vessel rupture determined by P-selectin expression 60 CHAPTER 3 PARAMETRIC STUDY OF FOCUSED ULTRASOUND AND MICROBUBBLES 67 3.1 Methodology 70 3.1.1 Materials 70 3.1.2 Synthesis of lipid-coated CdSe quantum dot nanoparticles (LQDs) 70 3.1.3 Cell culture 72 3.1.4 Experimental animals 72 3.1.5 Ultrasound system 73 3.1.6 Experimental protocols 76 3.1.6.1 Microbubbles (MBs) 79 3.1.6.2 Accumulation of LQD nanoparticles with time 80 3.1.6.3 Duration of FUS sonication 81 3.1.6.4 Treatment-procedure sequence 81 3.1.7 Quantitative determination of LQD nanoparticles deposited in tumor tissue with graphite furnace atomic absorption spectrometry (GF-AAS) 82 3.1.8 Histological analysis 83 3.1.9 Temperature measurement 85 3.1.10 Statistical analysis 85 3.2 Results 86 3.2.1 Accumulation of LQD nanoparticles with time in sonicated tumor tissues 86 3.2.2 Effect of injected MB dose on the accumulation of LQD nanoparticlesin sonicated tumor tissues 88 3.2.3 Effect of FUS sonication duration on the accumulation of LQD nanoparticles in sonicated tumor tissues 90 3.2.4 Effect of treatment-procedure sequence on the accumulation of LQD nanoparticles in sonicated tumor tissues 92 3.2.5 Histological observations and nanoparticle fluorescence 94 3.3 Discussion 96 CHAPTER 4 CONCLUSIONS 103 CHAPTER 5 FUTURE WORK 105 REFERENCES 107 APPENDIX 117 | |
| dc.language.iso | en | |
| dc.title | 聚焦超音波結合微氣泡強化奈米顆粒在腫瘤組織累積之定量與定性及最佳參數分析研究 | zh_TW |
| dc.title | Investigation of Nanoparticle Accumulation in Tumor Tissues Enhanced by Focused Ultrasound with Microbubbles | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 張富雄(Fu-Hsiung Chang) | |
| dc.contributor.oralexamcommittee | 謝銘鈞(Ming-Jium Hsieh),林峰輝(Feng-Huei Lin),鄭文芳(Wen-Fang Cheng),林杰樑(Ja-Liang Lin),萬永亮(Yung-Liang Wan),江惠華(Hui-Hua Chiang),陳三元(San-Yuan Chen) | |
| dc.subject.keyword | 聚焦型超音波,超音波顯影劑,微氣泡,奈米顆粒,強化藥物輸送, | zh_TW |
| dc.subject.keyword | Focused ultrasound (FUS),Ultrasound contrast agent (UCA),Microbubbles,Lipid-coated quantum dots,Enhanced nanoparticle delivery, | en |
| dc.relation.page | 121 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-07-23 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| 顯示於系所單位： | 醫學工程學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-99-1.pdf 目前未授權公開取用 | 3.04 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。