氧化鐵奈米粒子之新穎性及其在治療上之應用

Optical property of Fe3O4 nanoparticles and its application in therapy

陳俐臻(Li-Chen Chen)

指導教授 ： 張富雄

國立臺灣大學/醫學院/生物化學暨分子生物學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.01195

摘要

具有光學性質的奈米粒子，被廣泛應用在許多研究與臨床檢測，當作細胞標定的探針，例如量子點、金奈米粒子、氧化鐵奈米粒子。量子點具有很穩定的螢光訊號，發光強且持久，在細胞標定上有很好的應用，但量子點對細胞具有高毒性，不適合用於活體偵測；金奈米粒子也具有螢光訊號，在醫療上可使用雷射激發高溫殺死癌細胞；氧化鐵奈米粒子對細胞不會產生毒性，具有磁性可作細胞分離、產生MRI訊號，在藥物遞送上，可藉由外在磁場引導氧化鐵奈米粒子到作用位置，達到治療效果。
金奈米粒子的螢光訊號是來自於表面電漿共振，而我們實驗室曾經偵測到氧化鐵奈米粒子的螢光訊號，但並未進一步去確認訊號是否存在以及發光機制，先前文獻中也未提到氧化鐵奈米粒子的螢光資訊，因此我針對氧化鐵奈米粒子作分析，確認是否具有光學特性，我們使用3β-[N-(2-guanidinoethyl)carbamoyl]cholesterol (GEC-Chol)與膽固醇混合製備成GEC-Chol/Chol奈米脂微粒(GCC)，包覆氧化鐵奈米粒子後，製成磁性奈米脂微粒，送入EMT- 6 小鼠乳腺癌細胞，使用共軛焦顯微鏡、多光子雷射激發系統偵測，在不同波長下皆可激發出螢光訊號，以及很強的倍頻訊號，且這些光學訊號在固定細胞或是活細胞中皆可偵測到，發展至活體臨床應用也相當具有潛力。而磁性奈米脂微粒所攜帶的氧化鐵奈米粒子越多，光學訊號也越強，代表這些光學訊號是來自氧化鐵奈米粒子而非脂質。
另一方面，許多文獻研究雷射激發金奈米粒子的光熱效應，使用雷射激發金奈米粒子產生高溫殺死癌細胞。氧化鐵奈米粒子同為金屬材質，之前也報導過利用磁場，可引發氧化鐵奈米粒子的磁炙效應，而我們發現雷射也可激發氧化鐵奈米粒子毒殺細胞，狀況與金奈米粒子雷同，詳細作用機制仍需進一步探討。
確定了氧化鐵奈米粒子的螢光訊號，我們要進一步確認此發光機制，以及修飾脂微粒表面，使其具有攜帶抗體的能力，專一性標靶特定受體表現的癌細胞，分辨出癌細胞跟正常細胞，也可攜帶藥物，用磁力引導到治療位置，使用雷射或是磁場激發熱治療效應，達到有效抗癌效果。

關鍵字

氧化鐵 ； 奈米粒子 ； 螢光特性 ； 光熱療法

並列摘要

Nanoparticles are widely applied in many studies and in clinical detections. Some nanoparticles such as quantum dots, gold nanorods and iron oxide nanoparticles have the physical or chemical property that is used as probes for cellular imaging. Quantum dots (QDs) have a quite stable, strong and persistent fluorescence signal that can be detected easily, due to their unique physical characteristics frequently used as optimal probe in cellular labeling, but their cytotoxic nature limited their use in vivo. Other nanoparticles that are used very often are gold nanorods. It has a fluorescence property that can be excited using an infrared-light laser for hyperthermia treatment. Due to this physical property, gold nanorods are often used in medical purposes for cancer therapy. Iron oxide nanoparticles are less toxic and its magnetic property is widely applied in many biological studies, such as cell separation, magnetic resonance imaging (MRI), drug delivery and electromagnetic heating.
Iron oxide nanoparticles and gold nanorods are commonly used metal nanoparticles for medical purposes. For example, the fluorescence intensity of gold nanorods results from surface plasmon resonance effect. However the optical properties of iron oxide nanoparticles are poorly investigated. Therefore in this study I focused to study the optical property, and explore its mechanism of these nanoparticles for future biological application.
We used GEC-Chol/Chol encapsulated magnetic nanomicelles composed of iron oxide nanoparticles, and delivered it into mouse EMT-6 cell line. Then I used the laser confocal microscope to analyze the fluorescence intensity and third harmonic generation signal. My results showed that iron oxide fluorescence signal is dependent on ammount of iron oxide nanoparticles dose. With this result, I demonstrated that the fluorescence signal significantly generated from iron oxide nanoparticles but not from lipid shells. Further studies should be carried for further understanding of the optical mechanism. Iron oxide nanoparticles have the advantage that can be used and easily detected in fixed or live cells. Their high biocompatibility and feasible formulation in clinical application was expected. We also used infrared-light laser to excite the magnetic nanomicells, it caused cancer cells death, nevertheless, the detail cell killing mechanism needs to be further explored.

並列關鍵字

ferrite ； nanoparticles ； fluorescence ； photo thermotherapy

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