利用磁性奈米粒子作為交變磁場造成熱治療之初步影響分析

Abstract

奈米粒子在近幾年來被廣泛應用在許多癌症治療，氧化鐵奈米粒子就是其中的一員，由於生物相容性高、特殊的磁性功能使得被廣泛應用在生物性研究上像是細胞標定、細胞分離、核磁共振、熱炙效應、遞送藥物等等。透過微脂粒包覆的氧化鐵奈米粒子有許多優點例如可以使得生物相容性提高、放置交變磁場下，可以產生熱炙效應進而達到治療的效果。腫瘤生長速度快，所以需要大量的養份提供，進而會分泌一些促進血管生成的因子像是VEGF、FGF 等等。促使周遭的血管沿伸至腫瘤處此種現象稱為血管新生，血管新生對於腫瘤的生長、遷移都是非常重要的，血管新生也可以被當作早期腫瘤偵測的指標及治療的目標。在本篇研究中利用小鼠耳朵腫瘤模式 (Mouse Ear Tumor Model)，對腫瘤進行觀察，因為耳朵薄且透光的特性，使得我們可以較容易觀測到腫瘤的生長及周圍的血管變化。我將正價脂質與膽固醇奈米化製成正價奈米微脂粒，並將此包覆氧化鐵奈米粒子，大小約為120~150 nm。並打入小鼠耳朵腫瘤進行實驗，實驗分成兩部分，第一部分將打入奈米粒子的小鼠放置於核磁共振儀器上觀測。第二部分將打入磁性奈米粒子的小鼠放置於200 高斯的交變磁場下，使磁性奈米 粒子產生熱炙效應進而對腫瘤產生抑制效果，觀察一星期後將小鼠犧牲，將腫瘤做切片處理觀察是否有治療效果。綜合以上結果：我透過小鼠耳朵腫瘤模式可以較方便及長時間的觀測腫瘤的生長變化。我們可以核磁共振儀器清楚觀測到磁性奈米粒子在腫瘤內的核磁共振訊號。.打入腫瘤的磁性奈米粒子可以在200 高斯的交變磁場下產生熱炙效應，雖然可以產生抑制生長的效果但是治療卻不顯著，原因可能為磁性奈米粒子的量太少或是產生的交變磁場不夠強。將來若可以提高打入磁性奈米粒子的量或是提升交變磁場產生的強度，可能可以將腫瘤的治療效果提升。

Nanoparticles are widely applied in many researches and cancer therapies. Superparamagnetic iron oxide nanoparticle (SPIO) which is lesstoxic and its magnetic property is widely applied in many biological studies,such as cell labeling, cell sorting, cell therapy, magnetic resonance imaging (MRI), hyperthermia, and drug delivery. Liposome encapsulated SPIO is called L-SPIOs. Recently L-SPIOs are widely used in disease therapy because of the advantages of L-SPIOs such as they have more biological compatibility, they can be modified with targeting ligand/antibody or magnetic field to promote specific targeting, they can induce hyperthermia on alternating magnetic field to apply in cancer therapy. Angiogenesis, new blood vessels sprouting from pre-existing vessels, is essential for tumor growth,invasion and metastasis. It can be used as a biomarker for early stage tumor diagnosis and targeted therapy. To visualize angiogenesis many molecular imaging modalities have been used. In this research, we used mouse ear model to observe tumor growth, and angiogenesis easily. GEC-Chol/chol was established were used to encapsulate SPIOs to formulate L-SPIOs which is about 120~150 nm in diameter. L-SPIOs were used with its magnetic property on MRI signal to study the nanoparticles distribution in mouse ear tumor model. In addition, I use L-SPIOs to induce hyperthermia on alternating magnetic field (AMF) to treatment cancer on this mouse ear tumor model. My results showed the mouse ear tumor can be suppressed growth on 200 Oe AMF and the suppressed affect can be dependent on amount of L-SPIOs dose. With this results , I can observe tumor easily and nanoparticle distribution on mouse ear tumor model. I also observed that L-SPIOs can affect tumor growth by hyperthermia.