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標題: | 穴蝕效應及輻射力在超音波血栓溶解及藥物傳輸所扮演的角色 Roles of Cavitation and Radiation Force in Sonothrombolysis and Drug Delivery |
作者: | Yueh-Hsun Chuang 莊岳勳 |
指導教授: | 李百祺 |
關鍵字: | 穴蝕效應,輻射力,血栓溶解,太平洋紫杉醇,乳癌, cavitation,radiation force,thrombolysis,paclitaxel,breast cancer, |
出版年 : | 2013 |
學位: | 博士 |
摘要: | 超音波穴蝕效應已經有很多研究嘗試運用在血栓溶解上,超音波輻射力可以使血管內皮細胞間隙變寬,及促進治療物質的傳送。首先,我們評估了結合穴蝕效應、微氣泡及鏈激酶對於血栓溶解的效應。我們發現溫度上升不能完全解釋酵素引發的血栓溶解效應,以及差異性惰性穴蝕效應劑量可以是一個有效的血栓溶解指標。第二部分則是對於穴蝕效應引發的血栓溶解效應,我們檢視了利用施加超音波輻射力對於聚集及標定微氣泡所產生的效果。我們的觀察也確定了輻射力可以幫助微氣泡分布到血栓內部,穴蝕效應也同樣可以。結合輻射力及穴蝕效應相對應於單純施加穴蝕效應,可以提供額外的血栓溶解效果。超音波輻射力所提供的局部傳遞效果,有潛力可以用來提高超音波血栓溶解的安全性及效果。第三部分我們假設了白蛋白微氣泡在不使用抗體作為專一性標定的情況下,可以針對乳癌細胞進行藥物傳送。我們同時也研究了超音波輻射力以及轉化生長因子TGF-β1,對於白蛋白微氣泡跟細胞之間互動的可能扮演角色。結果顯示白蛋白微氣泡可以進入乳癌細胞而且存活超過24小時,即使氣泡帶有太平洋紫杉醇藥物也可以。施加輻射力更可以增加這個現象的百分比。然而這個現象可以被轉化生長因子TGF-β1阻斷,即使後續施加輻射力也是如此。由此我們得到的結論是轉化生長因子TGF-β1的接受器應該有參與白蛋白微氣泡進入乳癌細胞的細胞吞噬作用。另外,白蛋白微氣泡在沒有抗體接合來輔助標定的情況下,依然可以是一個傳遞藥物的有效方法。整體來說,我們在此呈現的研究,主要展現了超音波輻射力及穴蝕效應對於血栓溶解及藥物傳遞上,扮演了不同且重要的角色。 Acoustic cavitation has been studied in application of thrombolysis. Radiation force induces gaps between endothelium and enhances the delivery of therapeutic substances. First, we evaluated the effects of cavitation, microbubbles (MBs), and streptokinase on thrombolysis. We found that temperature rise cannot fully explained enzymatic sonothrombolysis and the differential inertial cavitation dose is a good in-dicator. Second, we examined the efficacy of using radiation forces to localize and enhance the targeting of MBs in cavitation-induced sonothrombolysis. Our observations confirm that radiation forces help MBs to distribute into a clot (as does cavitation). Combining radiation forces with cavitation would provide additional thrombolysis effects relative to cavitation alone. A local delivery method based on radiation forces has the potential to improve the safety and efficacy of sonothrombolysis. Third, we hypothesized that albumin MBs can be used for drug delivery to breast cancer cells without antibody conjugation for specific targeting. We also studied the possible roles of TGF-β1 and a radiation force in the behavior of cells and albumin MBs. The results show that albumin MBs can enter breast cancer cells and remain therein for at least 24 hours, even in the presence of paclitaxel loading. Applying radiation force further increased the percentage. This process could be blocked by TGF-β1, even with subsequent exposure to the radiation force. From these results we conclude that TGF-β1 receptors are involved in endocytosis of albumin MBs entering breast cancer cells. The albumin MBs without antibody conjugation can be a useful method of drug delivery. The entire study we presented here demonstrates that radiation force and cavitation play different roles and are important in thrombolysis and drug delivery. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5905 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 電機工程學系 |
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