研究生: |
范植泰 Fan, Chih-Tai |
---|---|
論文名稱: |
多孔隙金桿磁奈米矽球作為多功能性光聲造影對比劑之研究 Magnetic porous nano-silica beads with pore-filled gold nanorods as multifunctional contrast agents of photoacoustic imaging |
指導教授: |
李夢麟
Li, Meng-Lin |
口試委員: |
葉秩光
Yeh, Chih-Kuang 劉浩澧 Liu, Hao-Li 沈哲州 Shen, Che-Chou |
學位類別: |
碩士 Master |
系所名稱: |
電機資訊學院 - 電機工程學系 Department of Electrical Engineering |
論文出版年: | 2012 |
畢業學年度: | 100 |
語文別: | 英文 |
論文頁數: | 78 |
中文關鍵詞: | 光聲造影 、分子影像 、腫瘤標靶 、奈米粒子 、磁力標靶 、金奈米桿 |
外文關鍵詞: | photoacoustic imaging, Molecular imaging, tumor targeting, nanoparticle, magnetic targeting, gold nanorod |
相關次數: | 點閱:2 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 |
在光聲造影下對腫瘤進行影像導引監控與相關治療,需要高穩定性與低劑量的對比劑作為輔助,以及需要提升對比劑在光聲造影下對病灶敏感度與對比度、體循環時間、光熱穩定性等功能。在本研究中,我們驗證一個創新的光聲對比劑的可行性:多孔隙金桿磁奈米矽球(簡稱金磁奈米海膽),藉由以金奈米桿的光學及光聲特性為基礎,結合二氧化矽載體的高生物相容性與光聲訊號強化能力,並進一步加上氧化鐵奈米粒子的磁力特性,來提升作為腫瘤標靶的能力。我們以仿體實驗確認其在紅外光600-900nm下的光波長可調性,於紅外光下可避免強血液訊號干擾,以及以雷射曝照確認了金磁奈米海膽具有高光熱穩定性,可維持光吸收峰值與吸收能力。同時在光聲影像下利用磁力標靶提高目標區域光聲對比度近17 dB,更發現了在超音波下形成團簇也具有提升影像對比的功能;更進一步地在活體小鼠實驗中,對腫瘤區域使用磁標靶,相較於金奈米桿僅有2 – 3 dB對比度,在光聲與超音波造影下,使用金磁奈米海膽我們可於活體腫瘤組織得到約10dB對比度的標定能力,驗證了多孔隙金桿磁奈米矽球作為腫瘤標靶的光聲對比劑可行性,未來將更進一步藉由訊號強度量化活體內對比劑累積濃度,並以影像導引的方式,進行光熱治療等研究。
Photoacoustic (PA) imaging requires contrast agents which can enhance the contrast and efficiency of tumor targeting, own high thermal stability and long circulation time, and are effective in low doses in vivo. In this study, we developed magnetic porous nano-silica beads with pore-filled gold nanorods (FeAuNSBs) as a multi-functional contrast agent of photoacoustic imaging. It owns the merits of gold nanorods with silica coating – high biocompatibility, PA signal amplification and optical tunability for PA signal generation. The magnetic property of its embedded iron oxide is used to improve tumor targeting, i.e., magnetic targeting. Phantom experiments were performed to confirm the tunability of FeAuNSB’s optical absorbance in near-infrared light, which ranges from 600-900nm, which allows us to avoid the interference of blood. Experiments with exposure of the phantom to laser pulses demonsrated the higher photothermal stability of FeAuNSBs. The wavelength of peak optical absorption was also sustained. The magnetic targeting property of FeAuNSBs enhanced the contrast in tumor regions by approximately 17 dB. It was also found that the FeAuNSB aggregation caused by magnetic targeting increased the contrast in ultrasound imaging. The in-vivo experimental results showed that with the magnet targeting to a tumor, we obtained a high contrast increase of about 10 dB over the targeted region in PA and US images, which is higher than 2 dB achieved using conventional AuNRs. Overall, we proved the feasibility of FeAuNSBs as a good tumor targeting contrast agent of PA imaging. Future work will focus on verification of FeAuNSB’s performance on photothermal therapy with PA image guidance.
H. Kobayashi et al., Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging, ACS Nano, vol.1 , p258-264 (2007)
M. Baker et al., Whole-animal imaging: the whole picture, Nature, vol.463 , p977–980 (2010)
H. Maeda et al., Vascular permeability enhancement in solid tumor various factors, mechanisms involved and its implications, International Immunopharmacology, vol.3, p319-328, (2003)
A. Z. Wang et al., Nanoparticle Delivery of Cancer Drugs, Annu. Rev. Med., vol.63, p185-198, (2012)
M. R. Dreher et al., Tumor Vascular Permeability, Accumulation, and Penetration of Macromolecular Drug Carriers, Journal of the National Cancer Institute, vol.98(5), p335-44, (2006)
H. Maeda et al., Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review, Journal of controlled release, vol.65, p271-84, (2000)
K. Cho, D. M. Shin et al., Therapeutic Nanoparticles for Drug Delivery in Cancer, Clin Cancer Res, vol.14(5), p1310-16, (2008)
F. Alexis, O. C. Farokhzad et al., Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles, Molecular Pharmaceutics, vol.5(4), p505-15, (2008)
Eun Chul Cho Dr. et al., The Effects of Size, Shape, and Surface Functional Group of Gold Nanostructures on Their Adsorption and Internalization by Cells, Small., vol.6(4), p517-22, (2010)
DA. Hume, The mononuclear phagocyte system, Curr. Opin. Immunol., vol.18, p49-53, (2006)
J. Wang et al., More Effective Nanomedicines through Particle Design, Small, vol.7(14), 1919-31, (2011)
J. Rao, Shedding Light on Tumors Using Nanoparticles, ACS Nano, vol.2(10), p1984-6, (2008)
A. A. Karabutov, N. B. Podymova, and V. S. Letokhov, Time-resolved laser optoacoustic tomography of inhomogeneous media, Appl. Phys. B, vol.63(6), p545–63, (1996)
R. O. Esenaliev et al., Sensitivity of laser opto-acoustic imaging in detection of small deeply embedded tumors, IEEE J. Sel. Top. Quantum Electron., vol.5(4), p981–8, (1999)
J. A. Viator et al., Photoacoustic measurement of epidermal melanin, Proc. SPIE, 4960, p14–20, (2003)
R. O. Esenaliev et al., Optoacoustic technique for noninvasive monitoring of blood oxygenation: a feasibility study , Appl. Opt., vol.41(22), p4722-31, (2002)
C.-W. Wei, S.-W. Huang, C.-R. C. Wang, and P.-C. Li, Photoacoustic flow measurements based on wash-in analysis of gold nanorods, IEEE Trans. Ultrason. Ferroelectr. Freq. Control, vol.54, p1131-41, (2007)
張晉嘉, “光聲定量血氧飽和濃度量測”, 國立清華大學電機工程研究所碩士學位論文, (2011)
M. Pramanik, L.-H. V. Wang et al., In vivo carbon nanotube-enhanced non-invasive photoacoustic mapping of the sentinel lymph node, Phys Med Biol., vol.54(11), p3291-301, (2009)
A.D.L. Zerda, S. S. Gambhir et al., Carbon nanotubes as photoacoustic molecular imaging agents in living mice, Nat Nanotechnol., vol.3(9), p557–62, (2008)
X. Sun et al., Nano-Graphene Oxide for Cellular Imaging and Drug Delivery, Nano Res, vol.1, p203-12, (2008)
G. Von Maltzahn et al., Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas, Cancer Res., vol.69, p3892-900, (2009)
C. M. Cobley, L.-H. Wang et al., Gold nanostructures: a class of multifunctional materials for biomedical applications, Chem. Soc. Rev., vol.40, p44-56, (2011)
M.-L. Li, L.-H. Wang et al., In-vivo photoacoustic microscopy of nanoshell extravasation from solid tumor vasculature, Journal of Biomedical Optics, vol.14, 010507, (2009)
M. Hu et al., Gold nanostructures: engineering their plasmonic properties for biomedical applications, Chem. Soc. Rev., vol.35, p1084-94, (2006)
J. Cheon, J.H. Lee, Synergistically integrated nanoparticles as multimodal probes for nanobiotechnology . Acc. Chem. Res., Vol.41 , p1630-40 (2008)
P.K. Jain, I. H. El-Sayed, M.A. El-Sayed, Au nanoparticles target cancer, Nano Today, vol.2 , p18-29 (2007)
Weissleder , R, Scaling down imaging: molecular mapping of cancer in mice, Nat Rev Cancer, vol.2 , p11-18 (2002)
H. Petrova et al., On the temperature stability of gold nanorods: comparison between thermal and ultrafast laser-induced heating, PCCP., vol.8(7), p814-21, 2006
Y.-S. Chen et al., Silica-Coated Gold Nanorods as Photoacoustic Signal Nanoamplifiers, Nano Letters, ver.9, 13/1/011, P6.55, (2006)
Y.-S. Chen et al., Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy, Optics express, vol.18(9), p8867-78, (2010)
P.-C. Li et al., In vivo photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods, Optics express, vol.16(23), p18605-15, (2008)
M.-Y. Hua, H.-L. Liu, H.-W. Yang, The effectiveness of a magnetic nanoparticle-based delivery system for BCNU in the treatment of gliomas, Biomaterials vol.32, p516-27, (2011)
E.I. Galanzha, V. P. Zharov et al., In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells, Nature nanotechnology, vol.4(12), p 855-60, (2009)
H.-L. Liu et al., Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain, PNAS., vol.107, p 15205-10, (2010)
J.-W. Kim, V.P. Zharov et al., Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents, Nature nanotechnology, vol.4, p688-694, (2009)
Y.-D. Jin et al., Multifunctional nanoparticles as coupled contrast agents, Nature communicatons, DOI: 10.1038, ncomms1042, (2010)
Y. Jung et al., Multifunctional nanoprobe to enhance the utility of optical based imaging techniques, Journal of Biomedical Optics, vol.17(1), 016015, (2012)
J. Lu, Biocompatibility, Biodistribution, and Drug-Delivery Efficiency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals, Small, vol.6(16), p1794–1805, (2010)
王柏勛, “高頻光聲影像系統及其小動物造影之應用”, 國立清華大學電機工程研究所碩士學位論文, (2009)
J. Liu, et al., Nanoparticles as image enhancing agents for ultrasonography. Physics in Medicine and Biology. vol.51(9), p2179-89, (2006)