研究生: |
鄭 煒 Cheng, Wei |
---|---|
論文名稱: |
具磁電操控表面電性之金奈米腦攜帶可穿透次級藥物載體應用於腦瘤深度治療 Penetrated Delivery of Drug to Deep Brain Tumor by Gold Nanobrain through Magnetoelectric Charge-Switchable Release |
指導教授: |
胡尚秀
Hu, Shang-Hsiu |
口試委員: |
劉定宇
Liu, Ting-Yu 萬德輝 Wan, De-Hui 姜文軒 Chiang, Wen-Hsuan |
學位類別: |
碩士 Master |
系所名稱: |
原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences |
論文出版年: | 2018 |
畢業學年度: | 106 |
語文別: | 英文 |
論文頁數: | 60 |
中文關鍵詞: | 多孔性金奈米粒子 、樹枝狀聚合物 、帕博西林 、外部磁場刺激釋放 、腫瘤穿透治療 、化療 |
外文關鍵詞: | Porous gold nanoparticles, Dendrimer, Palbociclib, Magnetoelectric charge-switchable release, Tumor penetration, Chemotherapy |
相關次數: | 點閱:138 下載:0 |
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在現今對於治療生長於主要器官和腦的癌症上,以手術方法往往都是不可行的,因此利用遠端控制釋放的藥物傳遞系統已經有多年的研究,另一方面奈米粒子在藥物傳遞上的發展,能達到高效率的腫瘤標靶和累積,因此結合奈米藥物載體和遠端控制釋放在腫瘤治療上是非常具有潛力的。然而,載體對於腫瘤的穿透能力往往是有限的,腫瘤組織的物理性屏障會降低治療效果,因此增強藥物載體的穿透能力是必須的。本研究中,我們製備出可以應用於外部磁場控制釋放的多孔性金奈米粒子,透過電子顯微鏡 (SEM和TEM) 的觀察可以看出金奈米粒子形狀類似大腦,交錯於表面的條狀構造讓奈米粒子具有孔洞性質,其粒徑可經由對苯二酚 (hydroquinone) 的調控,介於300到400奈米。另外更攜帶載負大量抗癌藥物帕博西林 (palbociclib) 的次級載體-樹枝狀聚合物,經由外部的高週波磁場刺激,這些次級載體能夠攜帶帕博西林穿透腫瘤微球及組織達到治療的目的,此外,多孔性金奈米腦裝載化療藥物/次級載體的裝載量 (loading capacity, LC) 和包覆率 (encapsulation efficiency, EE) 分別為54.3 %和57 %,從細胞實驗結果可以看到,在15和30分鐘的刺激下,細胞存活率可以從90 %降低到10 %。另外,在載體外部修飾上狂犬病蛋白以提升於大腦組織的累積量,提升5 %次級載體的累積量,達到標靶的目的,在動物的存活率實驗中更能延長動物的壽命達到6天。在組織和血液分析中,可以得知攜帶藥物的金奈米腦具有相當低的毒性。因此,經由多孔性金奈米腦搭載攜帶帕博西林的樹枝狀聚合物是非常具有潛力的藥物傳遞平台,能夠經由外部高週波磁場的刺激釋放達到有效的癌症抑制,對於腫瘤的非侵入性治療是非常不錯的選擇。
With the development of drugs encapsulated carriers effectively target and accumulate in cancer cells, the cooperation of nano-therapeutics and remote controlled release are considered as a promising way for tumor treatment. However, the limited ability of tumor penetration due to the physiological barrier of the tumor will restrict efficacy of treatment. Thus, the improvement of nanocarriers on penetrated delivery is needed. In this study, we developed a brain-like porous gold nanoparticle based vehicle as a magnetoelectric agent with high cargo payload. The diameter of the gold nanobrain (GNB) is tunable by altering the concentration of hydroquinone, which range from 300 nm to 400 nm. The cargo is PAMAM dendrimers loaded with cell cycle G1-inhibitor Palbociclib, which can be released under HFMF treatment. The secondary carrier managed to penetrate into tumor spheroids and tumor tissues and deliver Palbociclib for treatment. The loading capacity (LC) and encapsulation efficiency (EE) of GNB encapsulated with Palbociclib-loaded dendrimers (Pal-Den@GNB) were 54.3 % and 57 % respectively. The result of in vitro experiment showed that the viabilities of ALTS1C1 cell line reduced to 10 %. Moreover, with the assistant of RVG, the accumulation of secondary carrier in tumor increased and successfully prolonged the survival rate of brain tumor bearing mice to 6 days. In addition, RVG-Pal-Den@GNB showed low toxicity according to histochemistry and blood analysis. This magnetoelectric release of tumor penetrated delivery platform exhibited excellent performance on tumor inhibition and have a potential for non-invasive treatment application.
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