局部藥物傳輸搭載二氧化鈦奈米粒子的凝膠合併紫外光與放射治療增強對惡性膠質瘤的協同抗癌作用

Abstract

惡性膠質瘤是一種高度侵襲性的腦癌，其死亡率相當高，而存活率相對較低。目前，治療惡性膠質瘤的標準方法包括手術、放射治療和抗癌藥物的結合，然而，這些治療方式仍存在挑戰。首先，血腦障壁使得靜脈注射之治療藥物難以有效地到達腦中腫瘤部位。其次，正常腦組織的耐受性限制了可給予的放射劑量。本研究中，我們希望探討將二氧化鈦奈米粒子與紫外光及放射治療結合使用，透過其效力和便利性，以促進對惡性膠質瘤的協同效應。二氧化鈦奈米粒子具有獨特的性質，使其在各種應用中具有優勢，但此材料也能與生物系統相互作用，透過光刺激誘導活性氧的生成。然而，二氧化鈦奈米粒子結合紫外光與放射治療照射惡性膠質瘤的抗癌效果尚未確定，本研究旨在利用上述治療模式，探討協同增強其抗癌的效果。在我們的研究中，使用ALTS1C1細胞和各類動物模型來驗證二氧化鈦奈米粒子結合紫外光與放射治療的抗癌效果。研究顯示，二氧化鈦奈米粒子對惡性膠質瘤細胞既具有光增敏劑又具有放射增敏劑的作用。它通過生成活性氧來誘導DNA鏈斷裂，最終導致細胞凋亡。透過小鼠腫瘤模型的體內實驗，我們證實了局部藥物傳輸搭載二氧化鈦奈米粒子的凝膠合併紫外光與放射治療，不僅能透過協同抗癌效果有效抑制腫瘤生長，還在活體中顯示高生物相容性。

Malignant gliomas are associated with a highly aggressive form of brain cancer. The death rate for malignant gliomas, is unfortunately quite high, and the survival rates are relatively low. At present, the standard approach to treatment of malignant gliomas involves the combination of surgery, radiotherapy (RT) and anticancer agents, yet there are challenges exist in this treatment modality. Firstly, the blood-brain barrier (BBB) acts as a hindrance, making it challenging to deliver therapeutic agents effectively to the tumor site. Secondly, the tolerance of normal brain tissue sets a constraint on the overall radiation dosage that can be administered. In this study, we would like to investigate the effectiveness and convenience of treatment, combing titanium dioxide (TiO2) nanoparticles with ultraviolet (UV) irradiation and RT to facilitate the synergistic effect for malignant gliomas. TiO2 nanoparticles have unique properties that make them useful in various applications, but they can also interact with biological systems, potentially leading to the generation of reaction oxygen species (ROS). However, the anticancer effect on malignant gliomas of TiO2 combined with UV irradiation and RT remained undetermined. This research aims to employ TiO2 to synergistically enhance the anticancer effects when combined with both radiation and UV irradiation. In our study, we utilized ALTS1C1 cells and animal tumor models to demonstrate the anticancer effect of combined treatment of TiO2 along with UV irradiation and RT. Our observations indicate that TiO2 serves as both photosensitizer and radiosensitizer for glioma cells. It inhibits tumor proliferation by inducing DNA strand break through the generation of ROS, ultimately resulting in apoptosis. Trough in vivo experiment by mouse tumor model, we proved that the combination treatment involving TiO2-loaded CMC gel, UV irradiation, and RT can not only effectively inhibits tumor growth by synergistic anticancer effects but also exhibits biocompatibility in living body.