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

范植泰(Chih-Tai Fan)

指導教授 ： 李夢麟

國立清華大學/電機資訊學院/電機工程學系/碩士(2012年)

摘要

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。

關鍵字

光聲造影 ； 分子影像 ； 腫瘤標靶 ； 奈米粒子 ； 磁力標靶 ； 金奈米桿

並列摘要

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.

並列關鍵字

photoacoustic imaging ； Molecular imaging ； tumor targeting ； nanoparticle ； magnetic targeting ； gold nanorod

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