超音波驅動氣泡包埋奈米複合材料之多重成像及癌症治療

Ultrasound Driving Nanobubbles Embedded Nanocomposites for Multi-Imaging and Cancer Therapy

潘郁庭(Yu-Ting Pan)

指導教授 ： 劉如熹

國立臺灣大學/理學院/化學研究所/碩士(2017年)

https://doi.org/10.6342/NTU201700982

摘要

據衛福部統計，惡性腫瘤為國人死亡率之首，故癌症之預防、診斷與治療為目前醫療重大課題。現今醫學檢測方面因各種顯影效果皆有其優缺點，為使多種顯影效果於一種材料中同時發揮其優點，目前發展趨勢為使材料具多重成像之功能，能於各種成像條件下互相彌補不足之處，使檢測結果更加精確。此外，目前研究多傾向以單次注射之方式同時於顯影時進行治療達到雙重效果。
本研究將上轉換奈米粒子(upconversion nanoparticles)與石墨相氮化碳量子點(graphitic carbon nitride quantum dots)結合並包埋於奈米氣泡(nanobubbles)內，使用奈米氣泡之超音波影像與上轉換奈米粒子之螢光顯影以應用於多重顯影，超音波顯影具非侵入性、無放射性、穿透度高及其可得即時性影像之特性，目前廣泛使用於醫療臨床診斷中，但其解析度較差，因此須使用對比劑以提升影像對比度。上轉換奈米粒子可應用於螢光生物顯影，其螢光顯影之靈敏度高，同時亦兼具奈米載體之功能，將光敏藥物載入生物體內並標定於特定組織，但須以近紅外光激發，且其於組織穿透深度最深約15 mm，於此研究中結合螢光及超音波顯影達到多重成像之效果，解決螢光穿透深度不足及超音波之解析度不佳之問題。
本研究以808 nm近紅外光雷射照射於樣品後，上轉換奈米粒子受808 nm近紅外光激發，放出螢光與紫外光，將紫外光之能量傳遞予石墨相氮化碳後產生活性氧物質。實驗過程以超音波促使氣泡破裂，釋放出其中之上轉換奈米複合材料與活性氧物質，同時透過產生之活性氧物質應用於光動力治療，進而導致癌症細胞凋亡。此外，於奈米氣泡內添加3.5%之氧氣，以改善癌症細胞缺氧問題並大幅提升光動力治療之效果。

關鍵字

超音波 ； 奈米氣泡 ； 上轉換奈米粒子 ； 光動力治療 ； 多重顯影

並列摘要

Multiple imaging is an efficient way to meet the requirements of medical diagnosis. Different types of medical diagnosis have various advantages and disadvantages. In order to simultaneously perform different methods of diagnosis in a material to exploit their advantages, current development is focusing on making materials with multiple imaging function. The results arising from the different diagnostic techniques are complementary and therefore more accurate. Additionally, the current study can achieve the dual effect of bio-imaging and therapy via a single injection.
This study investigated a nanomaterial of 808 nm upconversion nanoparticles (NaYF4:Yb/Tm@NaYF4:Yb/Nd) with graphitic carbon nitride (g-C3N4) embedded in nanobubbles for multiple imaging and photodynamic therapy. When 808 nm laser was irradiated on the nanomaterial, upconversion nanoparticles emitted ultraviolet and visible light. The ultraviolet light excited graphitic carbon nitride generating reactive oxygen species (ROS). Then, we used ultrasound to rupture nanobubbles, so the released reactive oxygen species could stimulate cancer cell apoptosis. The combination of nanobubbles and upconversion nanoparticles solve the poor resolution of ultrasound imaging and the lack of penetration of fluorescent imaging. Moreover, adding 3.5% oxygen significantly enhances the effect of photodynamic therapy.

並列關鍵字

nanobubbles ； upconversion nanoparticles, graphitic carbon nitride, ultrasound imaging ； photodynamic therapy

參考文獻

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