合成磷酸鈣磁性奈米粒子於癌症熱療之應用

Abstract

腫瘤熱治療是目前非常熱門的研究題目，而許多新型的磁性奈米粒子也被研發出來，作為熱治療的熱種子（thermal seeds）。在本論文的第一部份，我們嘗試以氫氧基磷灰石（hydroxyapatite）為基底之磁性奈米粒子（magnetic hydroxyapatite nanoparticles，簡稱 mHAP）做為熱種子，注射入小鼠皮下腫瘤附近。結果於15天的觀察期內，只有注射mHAP及置入高頻交互磁場之小鼠，其腫瘤會在五天內迅速縮小。並且老鼠犧牲後之血清測試證明mHAP之毒性甚低。 第二部分則是以雙水雙鈣磷酸鹽dicalcium phosphate dihydrate (DCPD)為基底合成新的磁性奈米粒子（mDCPD），隨著不同的鐵含量被加入，其所表現的物理化學性質皆有顯著的不同，可以用X光散射 x-ray diffraction (XRD), 感應耦合電漿發射光譜分析儀inductively coupled plasma-optical emission spectrometer (ICP-OES), 超導量子干涉儀superconducting quantum interference device (SQUID), 和穿透式電子顯微鏡transmission electron microscopy (TEM)來檢查。加熱效率也在可接受之範圍內。細胞毒性測試(WST-1 and LDH assay)亦顯示其無毒性。在體外試驗中，mDCPD能顯著地殺死癌細胞而不損傷正常細胞。

Hyperthermia therapy for cancer has drawn more and more attention these days. Many different types of magnetic particles have been developed for the purpose of hyperthermia cancer therapy. In the first part, we conducted an in vivo cancer hyperthermia study of the new magnetic hydroxyapatite nanoparticles (mHAP) on a mouse model. Only the mice which were injected with mHAP and had been treated inside the magnetic field showed dramatic reduction of tumor volume, in the 15-day observation period. No local recurrence was noted. Therefore, our new magnetic hydroxyapatite nanoparticles have demonstrated therapeutic effect in a mouse model with little toxicity. In the second part, a magnetic nanoparticle based on dicalcium phosphate dihydrate (DCPD) was formed by co-precipitation method. Addition of different concentrations of ferrous chloride to DCPD can alter its material properties. Various physical, chemical and magnetic tests of the magnetic DCPD nanoparticles (mDCPD) were performed, including x-ray diffraction (XRD), inductively coupled plasma-optical emission spectrometer (ICP-OES), superconducting quantum interference device (SQUID), and transmission electron microscopy (TEM). The heating efficiency of mDCPD in alternating magnetic field was proved to be suitable for hyperthermia. The results of cytotoxicity tests (WST-1 and LDH assay) showed no harmful effect. The mDCPD showed relative cancer-killing ability without damaging normal cells in vitro.