神經膠質瘤(glioma)是成人神經中樞系統腫瘤中最常見的原發性腫瘤(primary neoplasms)，佔所有原發性神經中樞系統腫瘤中的63%。其中多形惡性神經膠質瘤(glioblastoma multiforme)是最具侵略性的神經膠質瘤之一。傳統上以外科手術切除、放射治療和化學藥物治療等方式來治療神經膠質瘤，但由於膠質母細胞瘤的侵襲能力很強，手術方法無法完全清除所有腫瘤極易復發。而放療與化療方法不具靶向性，對於人體正常組織也會造成損傷，造成極大的副作用。近年來，利用藥物遞送系統(drug delivery system)將藥物遞送到病灶處是熱門的領域。但就治療神經膠質瘤而言，藥物需通過血腦障壁(blood brain barrier)才能到達癌組織。由前人的研究發現，病原體雖然是大分子，卻可以透過「特洛伊木馬」(Trojan horse)的途徑以巨噬細胞為「木馬」穿越血腦障壁到達大腦內部。本研究利用β-葡聚醣作為藥物的載體，將β-葡聚醣與臨床上治療神經膠質瘤的藥物Temozolomide形成前藥(prodrug)，前藥中β-葡聚醣與臨床性藥Temozolomide主要以雙硫鍵鍵結，當口服β-葡聚醣與Temozolomide為前藥口服之後，到小腸之後被小腸上的巨噬細胞吞噬進入血液迴圈最後透過「特洛伊木馬」的途徑，將藥物遞送到腦腫瘤組織中。當到達腫瘤組織時，由於腫瘤組織富含穀胱甘肽(Glutathione, GSH)，可將雙硫鍵切斷，並將Temozolomide釋放出來，達到毒殺腫瘤組織的效果。本研究的實驗方法透過體外實驗培養模擬腫瘤組織的3D細胞球，證實巨噬細胞確實可以將藥物吞噬，浸潤到腫瘤組織內部。並在體外證實前藥可以有效的殺死腫瘤。同時利用口服的方式給予老鼠前藥的治療，並且透過觀察腫瘤大小的改變、老鼠體重的變化來觀察治療的療效。

Gliomas are the most common primary neoplasm in central nervous system tumor of adult, accounting for 63% of all the tumor in primary central nervous system. Among them, glioblastoma multiforme is one of the most aggressive gliomas. Traditionally, the gliomas are treated by surgery, radiotherapy and chemotherapy. However, due to the strong invasiveness of glioblastomas, the surgery cannot completely remove the tumor. Also, the radiotherapy and chemotherapy cause damage to normal tissues to cause great side effects. Therefore, these methods are not effective in killing brain tumor. In recent years, the use of “drug delivery systems” is a popular research area. However, for treating gliomas, the drugs need to pass through the blood brain barrier to reach the brain tumor, and it blocks large molecules to go through it. The studies in these years found that although the pathogen is a large molecule, it can go through the blood-brain barrier through “Trojan horses” pathway. Therefore, we use β-glucan as drug carrier to synthesize prodrug, and use temozolomide as clinical drug for treating glioma. Also, the temozolomide is bonded with β-glucan by disulfide bonds. After orally administrating with prodrug, the prodrug is engulfed by macrophages in the small intestine and go into the blood circulation. Finally, it passes through the blood brain barrier through "Trojan horse" pathway. When the prodrug reaches the tumors, the disulfide bond in prodrug will be cut by GSH, which is rich in tumor. In this way, the temozolomide will be released and kill the tumor cells. The method in our study culturing 3D cell spheroids to mimic tumors to confirm that macrophages can engulf the drug and infiltrate the tumors. Also, the mice were treated with the prodrug orally to know the efficacy of the treatment that was observed by measuring the in tumor size and the weight of mice.

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